Cutis

To the Editor:
A 12-year-old girl presented with discomfort and walking limitation caused by cutaneous masses on the plantar aspects of the feet with associated bone abnormalities that had started as several flesh-colored papules on the plantar surface of both feet at the age of 1 year. Over time the lesions gradually enlarged and formed irregular masses, more prominently on the right foot. At the age of 6 years, surgical correction was performed due to increased walking impairment and a skin examination that suggested connective tissue nevus. The results were good. However, the local tissue overgrowth recurred after 1 year. Slowly growing lesions were found at the surgical site, which necessitated hospitalization. Her medical history was negative for other disease. There was no family history of similar skin conditions and her parents were nonconsanguineous.

Physical examination revealed malnutrition and poor development in height as well as difficulty walking. She also had moderate scoliosis with a curve to the left. Dermatological examination showed multiple reddish cerebriform hyperplasia in both plantar areas; the right side was more severely involved (Figure 1A). There was macrodactyly of 2 toes on the right foot (Figure 1B). All results of routine blood examinations were within reference range. There were no abnormalities noted in the abdominal ultrasound and cardiac examinations. Plain radiographs of the spine and feet demonstrated scoliosis and exostosis on the calcaneus and bottom of the scaphoid. Histopathologic examination of tissue from the plantar cerebriform hyperplasia revealed hyperkeratosis, slight acanthosis and papillomatosis in the epidermis, and dense collagen bands and sparse elastic fibers in the dermis (Figure 2).

Given the clinical and radiologic manifestation, the diagnosis of Proteus syndrome (PS) was established. After taking into account the severe discomfort and the success of the first surgery, we performed a resection and full-thickness skin graft surgery once again. The feet recovered without any discomfort in daily life. The appearance of the skin graft area was normal 1 year following surgery (Figure 3). She was treated with spinal plate fixation at another institution, progressed well for 2 years, and was subsequently lost to follow-up.

Proteus syndrome is a multisystem disorder with a difficult diagnosis due to the variability of its manifestations. The worldwide incidence of this rare disorder is less than 1 per 1 million individuals, and it is thought to be caused by a somatic genetic alteration.¹ Clinical characteristics include bone abnormalities, vascular malformations, dysregulation of fatty tissue, linear verrucous epidermal nevus, and cerebriform connective tissue nevus (CCTN). Although CCTN is not a common finding in patients with PS, it is considered a fairly specific sign with the greatest impact for the diagnosis of PS.²

The general feature of PS--asymmetric disproportionate overgrowth of tissues--appears at 6 to 18 months of age, which makes it challenging to diagnose disease earlier. The CCTN in our patient was present since 1 year of age.

To make a diagnosis of PS, one must have all the general criteria and various specific criteria. The revised diagnostic criteria for PS are given in the Table.³ According to the diagnostic criteria, our patient fulfilled the mandatory general criteria and had plantar CCTN, epidermal nevus, and dysregulated adipose tissue. The CCTN has notable diagnostic value in mildly affected patients, as it is absent in diseases included in the differential diagnosis such as neurofibromatosis, Klippel-Trenaunay-Weber syndrome, Maffucci syndrome, and Bannayan-Riley-Ruvalcaba syndrome. Hemihyperplasia-multiple lipomatosis syndrome and CLOVES (congenital, lipomatous overgrowth, vascular malformations, epidermal nevi, and scoliosis/spinal/skeletal anomalies) syndrome also can present on the plantar surfaces, and lesions may be overgrown at birth but are softer and compressible, have wrinkles instead of deep folds, and tend to grow with the child rather than disproportionately as in PS.⁴

The epidermal nevi and vascular malformations generally do not spread or increase in number. In contrast, CCTN in PS grows throughout childhood but tends to remain stable in adulthood.⁴ Postponing surgical treatment until skin lesions stabilize appears to be the best option. However, for practical purposes, surgical intervention may be required at an earlier phase to address the severe functional and cosmetic consequences. Some patients require multiple orthopedic procedures over the ensuing years or decades to control the hyperplasia.³ New CCTN that developed from the prior surgical incision, macrodactyly of the fourth and fifth right toes, and scoliosis appeared when the patient came to our clinic for retreatment 1 year after the initial presentation. The asymmetrical and disproportionate overgrowth of tissues had moderately accelerated in that period. Considering the increasingly impaired walking, we performed a second surgery. On follow-up visits, the patient expressed improvement in daily life.

To the Editor:
A 12-year-old girl presented with discomfort and walking limitation caused by cutaneous masses on the plantar aspects of the feet with associated bone abnormalities that had started as several flesh-colored papules on the plantar surface of both feet at the age of 1 year. Over time the lesions gradually enlarged and formed irregular masses, more prominently on the right foot. At the age of 6 years, surgical correction was performed due to increased walking impairment and a skin examination that suggested connective tissue nevus. The results were good. However, the local tissue overgrowth recurred after 1 year. Slowly growing lesions were found at the surgical site, which necessitated hospitalization. Her medical history was negative for other disease. There was no family history of similar skin conditions and her parents were nonconsanguineous.

Physical examination revealed malnutrition and poor development in height as well as difficulty walking. She also had moderate scoliosis with a curve to the left. Dermatological examination showed multiple reddish cerebriform hyperplasia in both plantar areas; the right side was more severely involved (Figure 1A). There was macrodactyly of 2 toes on the right foot (Figure 1B). All results of routine blood examinations were within reference range. There were no abnormalities noted in the abdominal ultrasound and cardiac examinations. Plain radiographs of the spine and feet demonstrated scoliosis and exostosis on the calcaneus and bottom of the scaphoid. Histopathologic examination of tissue from the plantar cerebriform hyperplasia revealed hyperkeratosis, slight acanthosis and papillomatosis in the epidermis, and dense collagen bands and sparse elastic fibers in the dermis (Figure 2).

Given the clinical and radiologic manifestation, the diagnosis of Proteus syndrome (PS) was established. After taking into account the severe discomfort and the success of the first surgery, we performed a resection and full-thickness skin graft surgery once again. The feet recovered without any discomfort in daily life. The appearance of the skin graft area was normal 1 year following surgery (Figure 3). She was treated with spinal plate fixation at another institution, progressed well for 2 years, and was subsequently lost to follow-up.

Proteus syndrome is a multisystem disorder with a difficult diagnosis due to the variability of its manifestations. The worldwide incidence of this rare disorder is less than 1 per 1 million individuals, and it is thought to be caused by a somatic genetic alteration.¹ Clinical characteristics include bone abnormalities, vascular malformations, dysregulation of fatty tissue, linear verrucous epidermal nevus, and cerebriform connective tissue nevus (CCTN). Although CCTN is not a common finding in patients with PS, it is considered a fairly specific sign with the greatest impact for the diagnosis of PS.²

The general feature of PS--asymmetric disproportionate overgrowth of tissues--appears at 6 to 18 months of age, which makes it challenging to diagnose disease earlier. The CCTN in our patient was present since 1 year of age.

To make a diagnosis of PS, one must have all the general criteria and various specific criteria. The revised diagnostic criteria for PS are given in the Table.³ According to the diagnostic criteria, our patient fulfilled the mandatory general criteria and had plantar CCTN, epidermal nevus, and dysregulated adipose tissue. The CCTN has notable diagnostic value in mildly affected patients, as it is absent in diseases included in the differential diagnosis such as neurofibromatosis, Klippel-Trenaunay-Weber syndrome, Maffucci syndrome, and Bannayan-Riley-Ruvalcaba syndrome. Hemihyperplasia-multiple lipomatosis syndrome and CLOVES (congenital, lipomatous overgrowth, vascular malformations, epidermal nevi, and scoliosis/spinal/skeletal anomalies) syndrome also can present on the plantar surfaces, and lesions may be overgrown at birth but are softer and compressible, have wrinkles instead of deep folds, and tend to grow with the child rather than disproportionately as in PS.⁴

The epidermal nevi and vascular malformations generally do not spread or increase in number. In contrast, CCTN in PS grows throughout childhood but tends to remain stable in adulthood.⁴ Postponing surgical treatment until skin lesions stabilize appears to be the best option. However, for practical purposes, surgical intervention may be required at an earlier phase to address the severe functional and cosmetic consequences. Some patients require multiple orthopedic procedures over the ensuing years or decades to control the hyperplasia.³ New CCTN that developed from the prior surgical incision, macrodactyly of the fourth and fifth right toes, and scoliosis appeared when the patient came to our clinic for retreatment 1 year after the initial presentation. The asymmetrical and disproportionate overgrowth of tissues had moderately accelerated in that period. Considering the increasingly impaired walking, we performed a second surgery. On follow-up visits, the patient expressed improvement in daily life.

To the Editor:
A 12-year-old girl presented with discomfort and walking limitation caused by cutaneous masses on the plantar aspects of the feet with associated bone abnormalities that had started as several flesh-colored papules on the plantar surface of both feet at the age of 1 year. Over time the lesions gradually enlarged and formed irregular masses, more prominently on the right foot. At the age of 6 years, surgical correction was performed due to increased walking impairment and a skin examination that suggested connective tissue nevus. The results were good. However, the local tissue overgrowth recurred after 1 year. Slowly growing lesions were found at the surgical site, which necessitated hospitalization. Her medical history was negative for other disease. There was no family history of similar skin conditions and her parents were nonconsanguineous.

Physical examination revealed malnutrition and poor development in height as well as difficulty walking. She also had moderate scoliosis with a curve to the left. Dermatological examination showed multiple reddish cerebriform hyperplasia in both plantar areas; the right side was more severely involved (Figure 1A). There was macrodactyly of 2 toes on the right foot (Figure 1B). All results of routine blood examinations were within reference range. There were no abnormalities noted in the abdominal ultrasound and cardiac examinations. Plain radiographs of the spine and feet demonstrated scoliosis and exostosis on the calcaneus and bottom of the scaphoid. Histopathologic examination of tissue from the plantar cerebriform hyperplasia revealed hyperkeratosis, slight acanthosis and papillomatosis in the epidermis, and dense collagen bands and sparse elastic fibers in the dermis (Figure 2).

Given the clinical and radiologic manifestation, the diagnosis of Proteus syndrome (PS) was established. After taking into account the severe discomfort and the success of the first surgery, we performed a resection and full-thickness skin graft surgery once again. The feet recovered without any discomfort in daily life. The appearance of the skin graft area was normal 1 year following surgery (Figure 3). She was treated with spinal plate fixation at another institution, progressed well for 2 years, and was subsequently lost to follow-up.

Proteus syndrome is a multisystem disorder with a difficult diagnosis due to the variability of its manifestations. The worldwide incidence of this rare disorder is less than 1 per 1 million individuals, and it is thought to be caused by a somatic genetic alteration.¹ Clinical characteristics include bone abnormalities, vascular malformations, dysregulation of fatty tissue, linear verrucous epidermal nevus, and cerebriform connective tissue nevus (CCTN). Although CCTN is not a common finding in patients with PS, it is considered a fairly specific sign with the greatest impact for the diagnosis of PS.²

The general feature of PS--asymmetric disproportionate overgrowth of tissues--appears at 6 to 18 months of age, which makes it challenging to diagnose disease earlier. The CCTN in our patient was present since 1 year of age.

To make a diagnosis of PS, one must have all the general criteria and various specific criteria. The revised diagnostic criteria for PS are given in the Table.³ According to the diagnostic criteria, our patient fulfilled the mandatory general criteria and had plantar CCTN, epidermal nevus, and dysregulated adipose tissue. The CCTN has notable diagnostic value in mildly affected patients, as it is absent in diseases included in the differential diagnosis such as neurofibromatosis, Klippel-Trenaunay-Weber syndrome, Maffucci syndrome, and Bannayan-Riley-Ruvalcaba syndrome. Hemihyperplasia-multiple lipomatosis syndrome and CLOVES (congenital, lipomatous overgrowth, vascular malformations, epidermal nevi, and scoliosis/spinal/skeletal anomalies) syndrome also can present on the plantar surfaces, and lesions may be overgrown at birth but are softer and compressible, have wrinkles instead of deep folds, and tend to grow with the child rather than disproportionately as in PS.⁴

The epidermal nevi and vascular malformations generally do not spread or increase in number. In contrast, CCTN in PS grows throughout childhood but tends to remain stable in adulthood.⁴ Postponing surgical treatment until skin lesions stabilize appears to be the best option. However, for practical purposes, surgical intervention may be required at an earlier phase to address the severe functional and cosmetic consequences. Some patients require multiple orthopedic procedures over the ensuing years or decades to control the hyperplasia.³ New CCTN that developed from the prior surgical incision, macrodactyly of the fourth and fifth right toes, and scoliosis appeared when the patient came to our clinic for retreatment 1 year after the initial presentation. The asymmetrical and disproportionate overgrowth of tissues had moderately accelerated in that period. Considering the increasingly impaired walking, we performed a second surgery. On follow-up visits, the patient expressed improvement in daily life.

The Diagnosis: Sister Mary Joseph Nodule

The umbilical skin biopsy revealed a moderately differentiated adenocarcinoma (Figure) that was positive for cytokeratin 20 and CDX2 and negative for cytokeratin 7 and transcription termination factor 1. The patient subsequently underwent computed tomography of the abdomen and pelvis, which showed multiple soft-tissue nodules on the greater omentum, a soft-tissue density at the umbilicus, and thickening of the gastric mucosa. An upper endoscopy was then performed, which revealed a large fungating ulcerated mass in the stomach. Biopsy of this mass showed an invasive moderately differentiated adenocarcinoma, which was ERBB2 (formerly HER2) negative. Histopathologically, these pleomorphic glands looked similar to the glands seen in the original skin biopsy. With this diagnosis of metastatic gastric adenocarcinoma, our patient chose palliative chemotherapy but declined precipitously and died 2 months after the initial skin biopsy of the umbilical lesion.

When encountering a patient with an umbilical lesion, it is important to consider benign and malignant lesions in the differential diagnosis. A benign lesion may include scar, cyst, pyogenic granuloma, hemangioma, umbilical hernia, endometriosis, polyp, abscess, or the presence of an omphalith.¹ Inflammatory dermatoses such as psoriasis or eczema also should be considered. Malignant lesions could be either primary or secondary, with metastatic disease being the most common.² Sister Mary Joseph nodule (SMJN) is the eponymgiven to an umbilical lesion representing metastatic disease. Sister Mary Joseph was a nurse and surgical assistant to Dr. William Mayo in Rochester, Minnesota, in what is now known as the Mayo Clinic. She is credited to be the first to observe and note the association between an umbilical nodule and intra-abdominal malignancy. Metastasis to the umbilicus is thought to occur by way of contiguous, hematogenous, lymphatic, or direct spread through embryologic remnants from primary cancers of nearby gastrointestinal or pelvic viscera. It is a rare cutaneous sign of internal malignancy, with an estimated prevalence of 1% to 3%.³ The most common primary cancer is gastric adenocarcinoma, though cases of metastasis from pancreatic, endometrial, and less commonly hematopoietic or supradiaphragmatic cancers have been reported.⁴ It is more common in women, likely due to the addition of gynecologic malignancies.¹

The use of dermoscopy has been advocated as an adjuvant tool in delineating benign and malignant umbilical lesions when an atypical polymorphous vascular pattern indicating neovascularization has been observed with neoplastic growth.⁵ Once a suspicious umbilical lesion is identified, the first step should be to obtain a skin biopsy or to use fine needle aspiration for cytology.⁶ Biopsy is especially relevant in the background of cancer history because SMJN may present with cancer recurrence.3 Once one of these is obtained, histological and immunohistochemical analysis will guide further workup and diagnosis of the umbilical lesion.

The importance of reviewing such cases lies in the variable presentation of cutaneous metastases such as SMJN and the grim prognosis that accompanies this finding. It presents as a firm indurated plaque or nodule that may present with systemic symptoms suggestive of malignancy, though in 30% of cases it is the sole initial sign.⁷ The nodule may be painful if ulcerated or fissured. Bloody, serous, or purulent discharge may be present. After diagnosis of an SMJN, most patients succumb to the disease within 12 months. Thus, it is vital for dermatologists to investigate umbilical lesions with great caution and a high index of suspicion.

The Diagnosis: Sister Mary Joseph Nodule

The umbilical skin biopsy revealed a moderately differentiated adenocarcinoma (Figure) that was positive for cytokeratin 20 and CDX2 and negative for cytokeratin 7 and transcription termination factor 1. The patient subsequently underwent computed tomography of the abdomen and pelvis, which showed multiple soft-tissue nodules on the greater omentum, a soft-tissue density at the umbilicus, and thickening of the gastric mucosa. An upper endoscopy was then performed, which revealed a large fungating ulcerated mass in the stomach. Biopsy of this mass showed an invasive moderately differentiated adenocarcinoma, which was ERBB2 (formerly HER2) negative. Histopathologically, these pleomorphic glands looked similar to the glands seen in the original skin biopsy. With this diagnosis of metastatic gastric adenocarcinoma, our patient chose palliative chemotherapy but declined precipitously and died 2 months after the initial skin biopsy of the umbilical lesion.

When encountering a patient with an umbilical lesion, it is important to consider benign and malignant lesions in the differential diagnosis. A benign lesion may include scar, cyst, pyogenic granuloma, hemangioma, umbilical hernia, endometriosis, polyp, abscess, or the presence of an omphalith.¹ Inflammatory dermatoses such as psoriasis or eczema also should be considered. Malignant lesions could be either primary or secondary, with metastatic disease being the most common.² Sister Mary Joseph nodule (SMJN) is the eponymgiven to an umbilical lesion representing metastatic disease. Sister Mary Joseph was a nurse and surgical assistant to Dr. William Mayo in Rochester, Minnesota, in what is now known as the Mayo Clinic. She is credited to be the first to observe and note the association between an umbilical nodule and intra-abdominal malignancy. Metastasis to the umbilicus is thought to occur by way of contiguous, hematogenous, lymphatic, or direct spread through embryologic remnants from primary cancers of nearby gastrointestinal or pelvic viscera. It is a rare cutaneous sign of internal malignancy, with an estimated prevalence of 1% to 3%.³ The most common primary cancer is gastric adenocarcinoma, though cases of metastasis from pancreatic, endometrial, and less commonly hematopoietic or supradiaphragmatic cancers have been reported.⁴ It is more common in women, likely due to the addition of gynecologic malignancies.¹

The use of dermoscopy has been advocated as an adjuvant tool in delineating benign and malignant umbilical lesions when an atypical polymorphous vascular pattern indicating neovascularization has been observed with neoplastic growth.⁵ Once a suspicious umbilical lesion is identified, the first step should be to obtain a skin biopsy or to use fine needle aspiration for cytology.⁶ Biopsy is especially relevant in the background of cancer history because SMJN may present with cancer recurrence.3 Once one of these is obtained, histological and immunohistochemical analysis will guide further workup and diagnosis of the umbilical lesion.

The importance of reviewing such cases lies in the variable presentation of cutaneous metastases such as SMJN and the grim prognosis that accompanies this finding. It presents as a firm indurated plaque or nodule that may present with systemic symptoms suggestive of malignancy, though in 30% of cases it is the sole initial sign.⁷ The nodule may be painful if ulcerated or fissured. Bloody, serous, or purulent discharge may be present. After diagnosis of an SMJN, most patients succumb to the disease within 12 months. Thus, it is vital for dermatologists to investigate umbilical lesions with great caution and a high index of suspicion.

The Diagnosis: Sister Mary Joseph Nodule

The umbilical skin biopsy revealed a moderately differentiated adenocarcinoma (Figure) that was positive for cytokeratin 20 and CDX2 and negative for cytokeratin 7 and transcription termination factor 1. The patient subsequently underwent computed tomography of the abdomen and pelvis, which showed multiple soft-tissue nodules on the greater omentum, a soft-tissue density at the umbilicus, and thickening of the gastric mucosa. An upper endoscopy was then performed, which revealed a large fungating ulcerated mass in the stomach. Biopsy of this mass showed an invasive moderately differentiated adenocarcinoma, which was ERBB2 (formerly HER2) negative. Histopathologically, these pleomorphic glands looked similar to the glands seen in the original skin biopsy. With this diagnosis of metastatic gastric adenocarcinoma, our patient chose palliative chemotherapy but declined precipitously and died 2 months after the initial skin biopsy of the umbilical lesion.

When encountering a patient with an umbilical lesion, it is important to consider benign and malignant lesions in the differential diagnosis. A benign lesion may include scar, cyst, pyogenic granuloma, hemangioma, umbilical hernia, endometriosis, polyp, abscess, or the presence of an omphalith.¹ Inflammatory dermatoses such as psoriasis or eczema also should be considered. Malignant lesions could be either primary or secondary, with metastatic disease being the most common.² Sister Mary Joseph nodule (SMJN) is the eponymgiven to an umbilical lesion representing metastatic disease. Sister Mary Joseph was a nurse and surgical assistant to Dr. William Mayo in Rochester, Minnesota, in what is now known as the Mayo Clinic. She is credited to be the first to observe and note the association between an umbilical nodule and intra-abdominal malignancy. Metastasis to the umbilicus is thought to occur by way of contiguous, hematogenous, lymphatic, or direct spread through embryologic remnants from primary cancers of nearby gastrointestinal or pelvic viscera. It is a rare cutaneous sign of internal malignancy, with an estimated prevalence of 1% to 3%.³ The most common primary cancer is gastric adenocarcinoma, though cases of metastasis from pancreatic, endometrial, and less commonly hematopoietic or supradiaphragmatic cancers have been reported.⁴ It is more common in women, likely due to the addition of gynecologic malignancies.¹

The use of dermoscopy has been advocated as an adjuvant tool in delineating benign and malignant umbilical lesions when an atypical polymorphous vascular pattern indicating neovascularization has been observed with neoplastic growth.⁵ Once a suspicious umbilical lesion is identified, the first step should be to obtain a skin biopsy or to use fine needle aspiration for cytology.⁶ Biopsy is especially relevant in the background of cancer history because SMJN may present with cancer recurrence.3 Once one of these is obtained, histological and immunohistochemical analysis will guide further workup and diagnosis of the umbilical lesion.

The importance of reviewing such cases lies in the variable presentation of cutaneous metastases such as SMJN and the grim prognosis that accompanies this finding. It presents as a firm indurated plaque or nodule that may present with systemic symptoms suggestive of malignancy, though in 30% of cases it is the sole initial sign.⁷ The nodule may be painful if ulcerated or fissured. Bloody, serous, or purulent discharge may be present. After diagnosis of an SMJN, most patients succumb to the disease within 12 months. Thus, it is vital for dermatologists to investigate umbilical lesions with great caution and a high index of suspicion.

I am a coauthor on a recent literature review (J Am Acad Dermatol. 2016;75:798.e7-805.e7) that addressed a common question regarding the use of systemic agents: What should a clinician do if a patient on one of these therapies has an upcoming elective surgery?

Treatment with systemic immunomodulatory agents commonly is employed in patients with moderate to severe plaque psoriasis and psoriatic arthritis. In these individuals, the concern is that surgery may carry an increased risk for infectious or surgical complications. Based on the available literature, my coauthors and I sought to create recommendations for the perioperative management of systemic immunosuppressive therapies in patients with psoriasis and psoriatic arthritis. We conducted a literature review to examine studies that addressed the use of methotrexate, cyclosporine, and biologic agents in patients undergoing surgery. A total of 46 studies were examined, nearly all retrospective studies in patients with inflammatory bowel disease and rheumatoid arthritis.

Based on level III evidence, we concluded that infliximab, adalimumab, etanercept, methotrexate, and cyclosporine can be safely continued through low-risk operations in patients with psoriasis and psoriatic arthritis. For moderate- and high-risk surgeries, a case-by-case approach should be taken based on the patient’s individual risk factors and comorbidities.

What’s the issue?

This study does not provide specific guidelines because of limited and conflicting literature. However, it does provide general guidelines that hopefully will be augmented in the future. How will you handle this situation when it arises in your practice?

We want to know your views! Tell us what you think.

I am a coauthor on a recent literature review (J Am Acad Dermatol. 2016;75:798.e7-805.e7) that addressed a common question regarding the use of systemic agents: What should a clinician do if a patient on one of these therapies has an upcoming elective surgery?

Treatment with systemic immunomodulatory agents commonly is employed in patients with moderate to severe plaque psoriasis and psoriatic arthritis. In these individuals, the concern is that surgery may carry an increased risk for infectious or surgical complications. Based on the available literature, my coauthors and I sought to create recommendations for the perioperative management of systemic immunosuppressive therapies in patients with psoriasis and psoriatic arthritis. We conducted a literature review to examine studies that addressed the use of methotrexate, cyclosporine, and biologic agents in patients undergoing surgery. A total of 46 studies were examined, nearly all retrospective studies in patients with inflammatory bowel disease and rheumatoid arthritis.

Based on level III evidence, we concluded that infliximab, adalimumab, etanercept, methotrexate, and cyclosporine can be safely continued through low-risk operations in patients with psoriasis and psoriatic arthritis. For moderate- and high-risk surgeries, a case-by-case approach should be taken based on the patient’s individual risk factors and comorbidities.

What’s the issue?

This study does not provide specific guidelines because of limited and conflicting literature. However, it does provide general guidelines that hopefully will be augmented in the future. How will you handle this situation when it arises in your practice?

We want to know your views! Tell us what you think.

I am a coauthor on a recent literature review (J Am Acad Dermatol. 2016;75:798.e7-805.e7) that addressed a common question regarding the use of systemic agents: What should a clinician do if a patient on one of these therapies has an upcoming elective surgery?

Treatment with systemic immunomodulatory agents commonly is employed in patients with moderate to severe plaque psoriasis and psoriatic arthritis. In these individuals, the concern is that surgery may carry an increased risk for infectious or surgical complications. Based on the available literature, my coauthors and I sought to create recommendations for the perioperative management of systemic immunosuppressive therapies in patients with psoriasis and psoriatic arthritis. We conducted a literature review to examine studies that addressed the use of methotrexate, cyclosporine, and biologic agents in patients undergoing surgery. A total of 46 studies were examined, nearly all retrospective studies in patients with inflammatory bowel disease and rheumatoid arthritis.

Based on level III evidence, we concluded that infliximab, adalimumab, etanercept, methotrexate, and cyclosporine can be safely continued through low-risk operations in patients with psoriasis and psoriatic arthritis. For moderate- and high-risk surgeries, a case-by-case approach should be taken based on the patient’s individual risk factors and comorbidities.

What’s the issue?

This study does not provide specific guidelines because of limited and conflicting literature. However, it does provide general guidelines that hopefully will be augmented in the future. How will you handle this situation when it arises in your practice?

We want to know your views! Tell us what you think.

Scalp psoriasis often is the initial presentation of psoriasis, and it can be one of the most challenging aspects of the disease. It can be difficult to treat for several reasons. First, hair can interfere with topical therapy reaching its site of action on the scalp. Second, facial skin also can be exposed to these treatments with the associated risk for adverse events. Finally, compliance often is difficult.

An evidence-based review published online on September 21 in the American Journal of Clinical Dermatology examined treatments for scalp psoriasis, including newer systemic therapies. Of 475 studies initially identified from PubMed and 845 from Embase (up to May 2016), the review included 27 clinical trials, 4 papers reporting pooled analyses of other clinical trials, 10 open-label trials, 1 case series, and 2 case reports after excluding non-English literature.

Wang and Tsai noted that few randomized controlled trials have been performed specifically in scalp psoriasis. The authors found that topical corticosteroids provide good effects and are usually recommended as first-line treatment. Calcipotriol–betamethasone dipropionate is more highly effective than either of its individual components.

The analysis also suggested that localized phototherapy is better than generalized phototherapy on hair-bearing areas. Methotrexate, cyclosporine, fumaric acid esters, and acitretin are well-recognized agents in the treatment of psoriasis, but they located no published randomized controlled trials specifically evaluating these agents in scalp psoriasis. Wang and Tsai also commented that biologics and new small-molecule agents show excellent effects on scalp psoriasis, but the high cost of these treatments mean they may be limited to use in extensive scalp psoriasis. They suggested that more controlled studies are needed for an evidence-based approach to scalp psoriasis.

What’s the issue?

Scalp psoriasis can be an isolated condition or may occur in association with more extensive disease. There has been increased attention to its treatment over the last several years, with several new options. What is your preferred approach to scalp psoriasis?

We want to know your views! Tell us what you think.

Scalp psoriasis often is the initial presentation of psoriasis, and it can be one of the most challenging aspects of the disease. It can be difficult to treat for several reasons. First, hair can interfere with topical therapy reaching its site of action on the scalp. Second, facial skin also can be exposed to these treatments with the associated risk for adverse events. Finally, compliance often is difficult.

An evidence-based review published online on September 21 in the American Journal of Clinical Dermatology examined treatments for scalp psoriasis, including newer systemic therapies. Of 475 studies initially identified from PubMed and 845 from Embase (up to May 2016), the review included 27 clinical trials, 4 papers reporting pooled analyses of other clinical trials, 10 open-label trials, 1 case series, and 2 case reports after excluding non-English literature.

Wang and Tsai noted that few randomized controlled trials have been performed specifically in scalp psoriasis. The authors found that topical corticosteroids provide good effects and are usually recommended as first-line treatment. Calcipotriol–betamethasone dipropionate is more highly effective than either of its individual components.

The analysis also suggested that localized phototherapy is better than generalized phototherapy on hair-bearing areas. Methotrexate, cyclosporine, fumaric acid esters, and acitretin are well-recognized agents in the treatment of psoriasis, but they located no published randomized controlled trials specifically evaluating these agents in scalp psoriasis. Wang and Tsai also commented that biologics and new small-molecule agents show excellent effects on scalp psoriasis, but the high cost of these treatments mean they may be limited to use in extensive scalp psoriasis. They suggested that more controlled studies are needed for an evidence-based approach to scalp psoriasis.

What’s the issue?

Scalp psoriasis can be an isolated condition or may occur in association with more extensive disease. There has been increased attention to its treatment over the last several years, with several new options. What is your preferred approach to scalp psoriasis?

We want to know your views! Tell us what you think.

Scalp psoriasis often is the initial presentation of psoriasis, and it can be one of the most challenging aspects of the disease. It can be difficult to treat for several reasons. First, hair can interfere with topical therapy reaching its site of action on the scalp. Second, facial skin also can be exposed to these treatments with the associated risk for adverse events. Finally, compliance often is difficult.

An evidence-based review published online on September 21 in the American Journal of Clinical Dermatology examined treatments for scalp psoriasis, including newer systemic therapies. Of 475 studies initially identified from PubMed and 845 from Embase (up to May 2016), the review included 27 clinical trials, 4 papers reporting pooled analyses of other clinical trials, 10 open-label trials, 1 case series, and 2 case reports after excluding non-English literature.

Wang and Tsai noted that few randomized controlled trials have been performed specifically in scalp psoriasis. The authors found that topical corticosteroids provide good effects and are usually recommended as first-line treatment. Calcipotriol–betamethasone dipropionate is more highly effective than either of its individual components.

The analysis also suggested that localized phototherapy is better than generalized phototherapy on hair-bearing areas. Methotrexate, cyclosporine, fumaric acid esters, and acitretin are well-recognized agents in the treatment of psoriasis, but they located no published randomized controlled trials specifically evaluating these agents in scalp psoriasis. Wang and Tsai also commented that biologics and new small-molecule agents show excellent effects on scalp psoriasis, but the high cost of these treatments mean they may be limited to use in extensive scalp psoriasis. They suggested that more controlled studies are needed for an evidence-based approach to scalp psoriasis.

What’s the issue?

Scalp psoriasis can be an isolated condition or may occur in association with more extensive disease. There has been increased attention to its treatment over the last several years, with several new options. What is your preferred approach to scalp psoriasis?

We want to know your views! Tell us what you think.

To the Editor:

A 34-year-old man presented with fever, easy bruising, and pancytopenia with increased peripheral blasts of 77%. Bone marrow biopsy showed hypercellular marrow with 80% to 90% involvement by acute promyelocytic leukemia (APL) with complex cytogenetics: 47,XY,t(4;17;18)(p16;q21,q25;q21.1),+8, ins(15;17)(q22;q21q25). He underwent induction chemotherapy with all-trans retinoic acid (ATRA) and idarubicin, which was complicated by differentiation syndrome that presented with fever and fluid retention. Discontinuation of ATRA and initiation of dexamethasone led to resolution of the symptoms. Complete hematologic and molecular remission was achieved after the induction chemotherapy.

Following a risk-adapted treatment protocol for consolidation therapy,¹ he underwent an uneventful first cycle of consolidation therapy. On day 15 of the second cycle of consolidation therapy with ATRA and mitoxantrone he was hospitalized with a fever (temperature, 38°C) in a setting of neutropenia (absolute neutrophil count [ANC], 0/µL [reference range, 1500–7200/µL]). He was empirically treated with ceftazidime and vancomycin and maintained on prophylactic acyclovir and fluconazole. Routine workup was negative for infection. He became afebrile within 24 hours. With negative infectious workup, vancomycin was discontinued on day 17. On day 33 he again developed a fever (temperature, 38.8°C) when the ANC started to recover (570/µL). A new skin rash was noted at this time. Physical examination revealed generalized, nonpruritic, tender, pink papules and plaques with dusky centers and central pustules on the trunk as well as the upper and lower extremities. The palms and soles were spared. The rash was somewhat reminiscent of Sweet syndrome (SS). No vesicles, bullae, or erosions were seen (Figure 1). Repeat blood and urine cultures and chest radiograph were unremarkable. Ceftazidime was discontinued due to concern of drug-associated rash. Within the next 48 hours, the patient developed rigors and a worsening rash that led to reinitiation of broad-spectrum antibiotic coverage with meropenem and vancomycin. Computed tomography of the chest, abdomen, and pelvis did not show any evidence of infection or other abnormalities. Skin biopsy showed an acute folliculitis and multiple foci of mixed granulomatous inflammation consisting of histiocytes, lymphocytes, and neutrophils with focal necrosis present in the dermis, dermis-subcutis junction, and subcutis (Figure 2). Diagnostic features of vasculitis were not seen. Viral cytopathic features were not identified. Tissue culture and special stains including Gram, acid-fast bacteria, and Grocott methenamine silver stains were negative for infectious organisms in the biopsy. Both direct fluorescent antibody study and cell cultures for varicella-zoster virus, cytomegalovirus, and herpes simplex virus also were negative.

In the absence of microorganisms on skin biopsy and low clinical suspicion of infection, vancomycin and meropenem were discontinued on day 35 and empiric treatment with oral prednisone 40 mg daily was initiated on day 38, which resulted in a rapid improvement of the patient’s rash within 24 hours with complete resolution after a 7-day course of prednisone. Notably, the patient manifested concomitant recovery of the ANC. The patient completed his last cycle of consolidation therapy with ATRA and idarubicin without further complications and remains in molecular remission.

Neutrophilic dermatoses (NDs) are a group of disorders characterized by neutrophilic cutaneous infiltration without evidence of infection. These entities include SS, pyoderma gangrenosum, subcorneal pustular dermatosis, erythema elevatum diutinum, and neutrophilic eccrine hidradenitis.² Neutrophilic dermatoses commonly present with acute onset of skin lesions and fever. Underlying systemic disease such as malignancy, inflammatory disease, autoimmune disease, pregnancy, and medications are known to be associated with ND. Although the rash clinically was reminiscent of SS, the histopathologic features were inconsistent with SS. Sweet syndrome typically presents with extensive monotonous neutrophilic infiltrates in the dermis. In this case, the neutrophilic infiltrates were localized and associated with the hair follicle, in the dermis and subcutis, and were accompanied by a granulomatous inflammation. Neutrophilic eccrine hidradenitis clinically is similar to SS and the distinction usually is made on the basis of histopathologic examination. Lack of the neutrophilic infiltrates within the eccrine secretary coils in our case did not support the diagnosis of neutrophilic eccrine hidradenitis.

Although the histopathologic features of the presented case were inconsistent with a particular subtype of ND, the clinical presentation and response to corticosteroids suggested that this unusual mixed inflammatory skin reaction might share a similar pathophysiologic mechanism.

A review of 20 patients with sterile neutrophilic folliculitis demonstrated an association with systemic diseases including cutaneous T-cell lymphoma, monoclonal gammopathy, Crohn disease, and autoimmune disorders.³ In acute myeloid leukemia, sterile neutrophilic folliculitis may be part of the initial presentation and responds to induction chemotherapy.⁴ An extensive search of PubMed articles indexed for MEDLINE using the search terms folliculitis, APL, and neutrophilic dermatoses did not reveal any prior reports of isolated neutrophilic folliculitis or mixed granulomatous reaction in patients with APL in molecular remission.

Although rare, cases of ATRA-induced SS have been reported. Some authors believe that SS in APL may represent a partial form of differentiation syndrome.⁵ Those cases usually occur during first induction. However, a recurrent episode of differentiation syndrome cannot be excluded in this patient.

A cutaneous reaction to chemotherapy with mitoxantrone as a cause also should be considered, given that the rash occurred only during the second cycle of consolidation therapy when mitoxantrone was used. However, this rash is rare in patients receiving mitoxantrone. The late onset of the rash from the time of last mitoxantrone administration argues against this diagnosis.

In summary, we describe an unusual presentation of a sterile mixed inflammatory skin reaction that occurred in a setting of neutrophil recovery following a second cycle of induction chemotherapy with ATRA and mitoxantrone for APL.

To the Editor:

A 34-year-old man presented with fever, easy bruising, and pancytopenia with increased peripheral blasts of 77%. Bone marrow biopsy showed hypercellular marrow with 80% to 90% involvement by acute promyelocytic leukemia (APL) with complex cytogenetics: 47,XY,t(4;17;18)(p16;q21,q25;q21.1),+8, ins(15;17)(q22;q21q25). He underwent induction chemotherapy with all-trans retinoic acid (ATRA) and idarubicin, which was complicated by differentiation syndrome that presented with fever and fluid retention. Discontinuation of ATRA and initiation of dexamethasone led to resolution of the symptoms. Complete hematologic and molecular remission was achieved after the induction chemotherapy.

Following a risk-adapted treatment protocol for consolidation therapy,¹ he underwent an uneventful first cycle of consolidation therapy. On day 15 of the second cycle of consolidation therapy with ATRA and mitoxantrone he was hospitalized with a fever (temperature, 38°C) in a setting of neutropenia (absolute neutrophil count [ANC], 0/µL [reference range, 1500–7200/µL]). He was empirically treated with ceftazidime and vancomycin and maintained on prophylactic acyclovir and fluconazole. Routine workup was negative for infection. He became afebrile within 24 hours. With negative infectious workup, vancomycin was discontinued on day 17. On day 33 he again developed a fever (temperature, 38.8°C) when the ANC started to recover (570/µL). A new skin rash was noted at this time. Physical examination revealed generalized, nonpruritic, tender, pink papules and plaques with dusky centers and central pustules on the trunk as well as the upper and lower extremities. The palms and soles were spared. The rash was somewhat reminiscent of Sweet syndrome (SS). No vesicles, bullae, or erosions were seen (Figure 1). Repeat blood and urine cultures and chest radiograph were unremarkable. Ceftazidime was discontinued due to concern of drug-associated rash. Within the next 48 hours, the patient developed rigors and a worsening rash that led to reinitiation of broad-spectrum antibiotic coverage with meropenem and vancomycin. Computed tomography of the chest, abdomen, and pelvis did not show any evidence of infection or other abnormalities. Skin biopsy showed an acute folliculitis and multiple foci of mixed granulomatous inflammation consisting of histiocytes, lymphocytes, and neutrophils with focal necrosis present in the dermis, dermis-subcutis junction, and subcutis (Figure 2). Diagnostic features of vasculitis were not seen. Viral cytopathic features were not identified. Tissue culture and special stains including Gram, acid-fast bacteria, and Grocott methenamine silver stains were negative for infectious organisms in the biopsy. Both direct fluorescent antibody study and cell cultures for varicella-zoster virus, cytomegalovirus, and herpes simplex virus also were negative.

In the absence of microorganisms on skin biopsy and low clinical suspicion of infection, vancomycin and meropenem were discontinued on day 35 and empiric treatment with oral prednisone 40 mg daily was initiated on day 38, which resulted in a rapid improvement of the patient’s rash within 24 hours with complete resolution after a 7-day course of prednisone. Notably, the patient manifested concomitant recovery of the ANC. The patient completed his last cycle of consolidation therapy with ATRA and idarubicin without further complications and remains in molecular remission.

Neutrophilic dermatoses (NDs) are a group of disorders characterized by neutrophilic cutaneous infiltration without evidence of infection. These entities include SS, pyoderma gangrenosum, subcorneal pustular dermatosis, erythema elevatum diutinum, and neutrophilic eccrine hidradenitis.² Neutrophilic dermatoses commonly present with acute onset of skin lesions and fever. Underlying systemic disease such as malignancy, inflammatory disease, autoimmune disease, pregnancy, and medications are known to be associated with ND. Although the rash clinically was reminiscent of SS, the histopathologic features were inconsistent with SS. Sweet syndrome typically presents with extensive monotonous neutrophilic infiltrates in the dermis. In this case, the neutrophilic infiltrates were localized and associated with the hair follicle, in the dermis and subcutis, and were accompanied by a granulomatous inflammation. Neutrophilic eccrine hidradenitis clinically is similar to SS and the distinction usually is made on the basis of histopathologic examination. Lack of the neutrophilic infiltrates within the eccrine secretary coils in our case did not support the diagnosis of neutrophilic eccrine hidradenitis.

Although the histopathologic features of the presented case were inconsistent with a particular subtype of ND, the clinical presentation and response to corticosteroids suggested that this unusual mixed inflammatory skin reaction might share a similar pathophysiologic mechanism.

A review of 20 patients with sterile neutrophilic folliculitis demonstrated an association with systemic diseases including cutaneous T-cell lymphoma, monoclonal gammopathy, Crohn disease, and autoimmune disorders.³ In acute myeloid leukemia, sterile neutrophilic folliculitis may be part of the initial presentation and responds to induction chemotherapy.⁴ An extensive search of PubMed articles indexed for MEDLINE using the search terms folliculitis, APL, and neutrophilic dermatoses did not reveal any prior reports of isolated neutrophilic folliculitis or mixed granulomatous reaction in patients with APL in molecular remission.

Although rare, cases of ATRA-induced SS have been reported. Some authors believe that SS in APL may represent a partial form of differentiation syndrome.⁵ Those cases usually occur during first induction. However, a recurrent episode of differentiation syndrome cannot be excluded in this patient.

A cutaneous reaction to chemotherapy with mitoxantrone as a cause also should be considered, given that the rash occurred only during the second cycle of consolidation therapy when mitoxantrone was used. However, this rash is rare in patients receiving mitoxantrone. The late onset of the rash from the time of last mitoxantrone administration argues against this diagnosis.

In summary, we describe an unusual presentation of a sterile mixed inflammatory skin reaction that occurred in a setting of neutrophil recovery following a second cycle of induction chemotherapy with ATRA and mitoxantrone for APL.

To the Editor:

A 34-year-old man presented with fever, easy bruising, and pancytopenia with increased peripheral blasts of 77%. Bone marrow biopsy showed hypercellular marrow with 80% to 90% involvement by acute promyelocytic leukemia (APL) with complex cytogenetics: 47,XY,t(4;17;18)(p16;q21,q25;q21.1),+8, ins(15;17)(q22;q21q25). He underwent induction chemotherapy with all-trans retinoic acid (ATRA) and idarubicin, which was complicated by differentiation syndrome that presented with fever and fluid retention. Discontinuation of ATRA and initiation of dexamethasone led to resolution of the symptoms. Complete hematologic and molecular remission was achieved after the induction chemotherapy.

Following a risk-adapted treatment protocol for consolidation therapy,¹ he underwent an uneventful first cycle of consolidation therapy. On day 15 of the second cycle of consolidation therapy with ATRA and mitoxantrone he was hospitalized with a fever (temperature, 38°C) in a setting of neutropenia (absolute neutrophil count [ANC], 0/µL [reference range, 1500–7200/µL]). He was empirically treated with ceftazidime and vancomycin and maintained on prophylactic acyclovir and fluconazole. Routine workup was negative for infection. He became afebrile within 24 hours. With negative infectious workup, vancomycin was discontinued on day 17. On day 33 he again developed a fever (temperature, 38.8°C) when the ANC started to recover (570/µL). A new skin rash was noted at this time. Physical examination revealed generalized, nonpruritic, tender, pink papules and plaques with dusky centers and central pustules on the trunk as well as the upper and lower extremities. The palms and soles were spared. The rash was somewhat reminiscent of Sweet syndrome (SS). No vesicles, bullae, or erosions were seen (Figure 1). Repeat blood and urine cultures and chest radiograph were unremarkable. Ceftazidime was discontinued due to concern of drug-associated rash. Within the next 48 hours, the patient developed rigors and a worsening rash that led to reinitiation of broad-spectrum antibiotic coverage with meropenem and vancomycin. Computed tomography of the chest, abdomen, and pelvis did not show any evidence of infection or other abnormalities. Skin biopsy showed an acute folliculitis and multiple foci of mixed granulomatous inflammation consisting of histiocytes, lymphocytes, and neutrophils with focal necrosis present in the dermis, dermis-subcutis junction, and subcutis (Figure 2). Diagnostic features of vasculitis were not seen. Viral cytopathic features were not identified. Tissue culture and special stains including Gram, acid-fast bacteria, and Grocott methenamine silver stains were negative for infectious organisms in the biopsy. Both direct fluorescent antibody study and cell cultures for varicella-zoster virus, cytomegalovirus, and herpes simplex virus also were negative.

In the absence of microorganisms on skin biopsy and low clinical suspicion of infection, vancomycin and meropenem were discontinued on day 35 and empiric treatment with oral prednisone 40 mg daily was initiated on day 38, which resulted in a rapid improvement of the patient’s rash within 24 hours with complete resolution after a 7-day course of prednisone. Notably, the patient manifested concomitant recovery of the ANC. The patient completed his last cycle of consolidation therapy with ATRA and idarubicin without further complications and remains in molecular remission.

Neutrophilic dermatoses (NDs) are a group of disorders characterized by neutrophilic cutaneous infiltration without evidence of infection. These entities include SS, pyoderma gangrenosum, subcorneal pustular dermatosis, erythema elevatum diutinum, and neutrophilic eccrine hidradenitis.² Neutrophilic dermatoses commonly present with acute onset of skin lesions and fever. Underlying systemic disease such as malignancy, inflammatory disease, autoimmune disease, pregnancy, and medications are known to be associated with ND. Although the rash clinically was reminiscent of SS, the histopathologic features were inconsistent with SS. Sweet syndrome typically presents with extensive monotonous neutrophilic infiltrates in the dermis. In this case, the neutrophilic infiltrates were localized and associated with the hair follicle, in the dermis and subcutis, and were accompanied by a granulomatous inflammation. Neutrophilic eccrine hidradenitis clinically is similar to SS and the distinction usually is made on the basis of histopathologic examination. Lack of the neutrophilic infiltrates within the eccrine secretary coils in our case did not support the diagnosis of neutrophilic eccrine hidradenitis.

Although the histopathologic features of the presented case were inconsistent with a particular subtype of ND, the clinical presentation and response to corticosteroids suggested that this unusual mixed inflammatory skin reaction might share a similar pathophysiologic mechanism.

A review of 20 patients with sterile neutrophilic folliculitis demonstrated an association with systemic diseases including cutaneous T-cell lymphoma, monoclonal gammopathy, Crohn disease, and autoimmune disorders.³ In acute myeloid leukemia, sterile neutrophilic folliculitis may be part of the initial presentation and responds to induction chemotherapy.⁴ An extensive search of PubMed articles indexed for MEDLINE using the search terms folliculitis, APL, and neutrophilic dermatoses did not reveal any prior reports of isolated neutrophilic folliculitis or mixed granulomatous reaction in patients with APL in molecular remission.

Although rare, cases of ATRA-induced SS have been reported. Some authors believe that SS in APL may represent a partial form of differentiation syndrome.⁵ Those cases usually occur during first induction. However, a recurrent episode of differentiation syndrome cannot be excluded in this patient.

A cutaneous reaction to chemotherapy with mitoxantrone as a cause also should be considered, given that the rash occurred only during the second cycle of consolidation therapy when mitoxantrone was used. However, this rash is rare in patients receiving mitoxantrone. The late onset of the rash from the time of last mitoxantrone administration argues against this diagnosis.

In summary, we describe an unusual presentation of a sterile mixed inflammatory skin reaction that occurred in a setting of neutrophil recovery following a second cycle of induction chemotherapy with ATRA and mitoxantrone for APL.

The Diagnosis: Lichen Striatus

Lichen striatus (LS) is an acquired and self-limited linear inflammatory dermatosis that most frequently occurs in children and less commonly in adults.^1-3 Clinically, it is characterized by the sudden onset of an eruption consisting of slightly pigmented, erythematous, flat-topped papules with minimal scaling. These papules quickly coalesce to form a linear band that extends along a limb, the trunk, or the face, within Blaschko lines.^1,4 In the adult form, patients tend to experience more diffuse lesions as well as severe pruritus with higher rates of relapse. It occasionally manifests in a dermatomal manner.¹ 

The differential diagnosis includes other linear acquired inflammatory dermatoses such as blaschkitis, lichen planus, inflammatory linear verrucous epidermal nevus, and psoriasis. Blaschkitis has been described as a rare dermatosis that occurs along the Blaschko lines, affecting adults preferentially over children. Controversy exists whether blaschkitis and lichen striatus are the same disease or 2 separate entities.⁵ Clinically, both blaschkitis and lichen striatus can present with multiple linear papules and vesicles predominantly on the trunk. In blaschkitis, there is a predilection for males, with an older mean age at onset of 40 years.⁵ Lesions quickly resolve over months with frequent relapse compared to lichen striatus, which can persist for months to years. 

Histopathologically, blaschkitis demonstrates spongiosis, usually without involvement of the adnexal structures. Lichenoid and spongiotic changes with adnexal extension are the hallmark features of lichen striatus. In our patient, biopsy showed several dense bandlike foci of lymphohistiocytic infiltrates along the dermoepidermal junction with spongiosis, basal cell liquefactive degeneration, and pigmentary incontinence (Figure 1). The focal areas were surfaced by parakeratotic and orthohyperkeratotic scale. Deep dermal perivascular and periadnexal extension was present (Figure 2). Periodic acid-Schiff stain was negative for fungi.

The pathogenesis of lichen striatus is not entirely understood, but it has been postulated that trauma, vaccinations, or viral infections may induce loss of immunologic tolerance to keratinocytes.¹ This loss of tolerance can result in a T cell-mediated autoimmune reaction against malpighian cells, which show genetic mosaicism and are arranged along Blaschko lines.^1,3 Familial cases also have been reported, suggesting that there may be an epigenetic mosaicism that contributes to this group of skin diseases.^6,7

Lichen striatus tends to resolve on its own after approximately 6 to 9 months.⁸ Treatment typically consists of application of topical corticosteroids.¹ Cases also have been successfully treated with tacrolimus and pimecrolimus.^1,8 Our patient was treated with a midpotency topical steroid with improvement of the appearance but not complete resolution.

The Diagnosis: Lichen Striatus

Lichen striatus (LS) is an acquired and self-limited linear inflammatory dermatosis that most frequently occurs in children and less commonly in adults.^1-3 Clinically, it is characterized by the sudden onset of an eruption consisting of slightly pigmented, erythematous, flat-topped papules with minimal scaling. These papules quickly coalesce to form a linear band that extends along a limb, the trunk, or the face, within Blaschko lines.^1,4 In the adult form, patients tend to experience more diffuse lesions as well as severe pruritus with higher rates of relapse. It occasionally manifests in a dermatomal manner.¹ 

The differential diagnosis includes other linear acquired inflammatory dermatoses such as blaschkitis, lichen planus, inflammatory linear verrucous epidermal nevus, and psoriasis. Blaschkitis has been described as a rare dermatosis that occurs along the Blaschko lines, affecting adults preferentially over children. Controversy exists whether blaschkitis and lichen striatus are the same disease or 2 separate entities.⁵ Clinically, both blaschkitis and lichen striatus can present with multiple linear papules and vesicles predominantly on the trunk. In blaschkitis, there is a predilection for males, with an older mean age at onset of 40 years.⁵ Lesions quickly resolve over months with frequent relapse compared to lichen striatus, which can persist for months to years. 

Histopathologically, blaschkitis demonstrates spongiosis, usually without involvement of the adnexal structures. Lichenoid and spongiotic changes with adnexal extension are the hallmark features of lichen striatus. In our patient, biopsy showed several dense bandlike foci of lymphohistiocytic infiltrates along the dermoepidermal junction with spongiosis, basal cell liquefactive degeneration, and pigmentary incontinence (Figure 1). The focal areas were surfaced by parakeratotic and orthohyperkeratotic scale. Deep dermal perivascular and periadnexal extension was present (Figure 2). Periodic acid-Schiff stain was negative for fungi.

The pathogenesis of lichen striatus is not entirely understood, but it has been postulated that trauma, vaccinations, or viral infections may induce loss of immunologic tolerance to keratinocytes.¹ This loss of tolerance can result in a T cell-mediated autoimmune reaction against malpighian cells, which show genetic mosaicism and are arranged along Blaschko lines.^1,3 Familial cases also have been reported, suggesting that there may be an epigenetic mosaicism that contributes to this group of skin diseases.^6,7

Lichen striatus tends to resolve on its own after approximately 6 to 9 months.⁸ Treatment typically consists of application of topical corticosteroids.¹ Cases also have been successfully treated with tacrolimus and pimecrolimus.^1,8 Our patient was treated with a midpotency topical steroid with improvement of the appearance but not complete resolution.

The Diagnosis: Lichen Striatus

Lichen striatus (LS) is an acquired and self-limited linear inflammatory dermatosis that most frequently occurs in children and less commonly in adults.^1-3 Clinically, it is characterized by the sudden onset of an eruption consisting of slightly pigmented, erythematous, flat-topped papules with minimal scaling. These papules quickly coalesce to form a linear band that extends along a limb, the trunk, or the face, within Blaschko lines.^1,4 In the adult form, patients tend to experience more diffuse lesions as well as severe pruritus with higher rates of relapse. It occasionally manifests in a dermatomal manner.¹ 

The differential diagnosis includes other linear acquired inflammatory dermatoses such as blaschkitis, lichen planus, inflammatory linear verrucous epidermal nevus, and psoriasis. Blaschkitis has been described as a rare dermatosis that occurs along the Blaschko lines, affecting adults preferentially over children. Controversy exists whether blaschkitis and lichen striatus are the same disease or 2 separate entities.⁵ Clinically, both blaschkitis and lichen striatus can present with multiple linear papules and vesicles predominantly on the trunk. In blaschkitis, there is a predilection for males, with an older mean age at onset of 40 years.⁵ Lesions quickly resolve over months with frequent relapse compared to lichen striatus, which can persist for months to years. 

Histopathologically, blaschkitis demonstrates spongiosis, usually without involvement of the adnexal structures. Lichenoid and spongiotic changes with adnexal extension are the hallmark features of lichen striatus. In our patient, biopsy showed several dense bandlike foci of lymphohistiocytic infiltrates along the dermoepidermal junction with spongiosis, basal cell liquefactive degeneration, and pigmentary incontinence (Figure 1). The focal areas were surfaced by parakeratotic and orthohyperkeratotic scale. Deep dermal perivascular and periadnexal extension was present (Figure 2). Periodic acid-Schiff stain was negative for fungi.

The pathogenesis of lichen striatus is not entirely understood, but it has been postulated that trauma, vaccinations, or viral infections may induce loss of immunologic tolerance to keratinocytes.¹ This loss of tolerance can result in a T cell-mediated autoimmune reaction against malpighian cells, which show genetic mosaicism and are arranged along Blaschko lines.^1,3 Familial cases also have been reported, suggesting that there may be an epigenetic mosaicism that contributes to this group of skin diseases.^6,7

Lichen striatus tends to resolve on its own after approximately 6 to 9 months.⁸ Treatment typically consists of application of topical corticosteroids.¹ Cases also have been successfully treated with tacrolimus and pimecrolimus.^1,8 Our patient was treated with a midpotency topical steroid with improvement of the appearance but not complete resolution.

The Diagnosis: Lipoid Proteinosis

Lipoid proteinosis (LP), also known as hyalinosis cutis et mucosae or Urbach-Wiethe disease, is a rare autosomal-recessive disorder. It is characterized by deposition of hyalinelike material in multiple organs including the skin, oral mucosa, larynx, and brain. The underlying defect is mutations in the extracellular matrix protein 1 gene, ECM1, which binds to various proteins (eg, perlecan, fibulins, matrix metalloproteinase 9) and plays a role in angiogenesis and epidermal differentiation.^1-4 

The clinical spectrum of LP is primarily related to respiratory, skin, and neurologic manifestations, but any organ involvement may be seen. A childhood-onset weak cry or hoarseness usually is the first clinical sign of LP due to infiltration of the laryngeal mucosa.^3-6 A thickened frenulum, which manifests as restricted tongue movements, is another reliable clinical sign of LP.⁷ In addition, yellow-white submucous infiltrates on other mucosal surfaces (eg, pharynx, tongue, soft palate, esophagus)(Figure 1), occlusion of the salivary ducts (recurrent parotitis), dental anomalies, and dental caries (Figure 2) also may be seen.^5,7

Histologically, deposition of eosinophilic homogeneous material is seen around the blood vessels and sweat glands as well as in the dermis and dermoepidermal junction (Figure 4).^1,5 Although most patients with LP have a slowly progressive benign course that stabilizes in early adult life, some morbidities and complications may occur (eg, rarely upper respiratory tract involvement can progress and require tracheostomy). There presently is no cure for LP, but some drugs (eg, oral dimethyl sulfoxide, etretinate, acitretin, penicillamine) and laser ablation/dermabrasion of papules are helpful in some cases.^1,7

The Diagnosis: Lipoid Proteinosis

Lipoid proteinosis (LP), also known as hyalinosis cutis et mucosae or Urbach-Wiethe disease, is a rare autosomal-recessive disorder. It is characterized by deposition of hyalinelike material in multiple organs including the skin, oral mucosa, larynx, and brain. The underlying defect is mutations in the extracellular matrix protein 1 gene, ECM1, which binds to various proteins (eg, perlecan, fibulins, matrix metalloproteinase 9) and plays a role in angiogenesis and epidermal differentiation.^1-4 

The clinical spectrum of LP is primarily related to respiratory, skin, and neurologic manifestations, but any organ involvement may be seen. A childhood-onset weak cry or hoarseness usually is the first clinical sign of LP due to infiltration of the laryngeal mucosa.^3-6 A thickened frenulum, which manifests as restricted tongue movements, is another reliable clinical sign of LP.⁷ In addition, yellow-white submucous infiltrates on other mucosal surfaces (eg, pharynx, tongue, soft palate, esophagus)(Figure 1), occlusion of the salivary ducts (recurrent parotitis), dental anomalies, and dental caries (Figure 2) also may be seen.^5,7

Histologically, deposition of eosinophilic homogeneous material is seen around the blood vessels and sweat glands as well as in the dermis and dermoepidermal junction (Figure 4).^1,5 Although most patients with LP have a slowly progressive benign course that stabilizes in early adult life, some morbidities and complications may occur (eg, rarely upper respiratory tract involvement can progress and require tracheostomy). There presently is no cure for LP, but some drugs (eg, oral dimethyl sulfoxide, etretinate, acitretin, penicillamine) and laser ablation/dermabrasion of papules are helpful in some cases.^1,7

The Diagnosis: Lipoid Proteinosis

Lipoid proteinosis (LP), also known as hyalinosis cutis et mucosae or Urbach-Wiethe disease, is a rare autosomal-recessive disorder. It is characterized by deposition of hyalinelike material in multiple organs including the skin, oral mucosa, larynx, and brain. The underlying defect is mutations in the extracellular matrix protein 1 gene, ECM1, which binds to various proteins (eg, perlecan, fibulins, matrix metalloproteinase 9) and plays a role in angiogenesis and epidermal differentiation.^1-4 

The clinical spectrum of LP is primarily related to respiratory, skin, and neurologic manifestations, but any organ involvement may be seen. A childhood-onset weak cry or hoarseness usually is the first clinical sign of LP due to infiltration of the laryngeal mucosa.^3-6 A thickened frenulum, which manifests as restricted tongue movements, is another reliable clinical sign of LP.⁷ In addition, yellow-white submucous infiltrates on other mucosal surfaces (eg, pharynx, tongue, soft palate, esophagus)(Figure 1), occlusion of the salivary ducts (recurrent parotitis), dental anomalies, and dental caries (Figure 2) also may be seen.^5,7

Histologically, deposition of eosinophilic homogeneous material is seen around the blood vessels and sweat glands as well as in the dermis and dermoepidermal junction (Figure 4).^1,5 Although most patients with LP have a slowly progressive benign course that stabilizes in early adult life, some morbidities and complications may occur (eg, rarely upper respiratory tract involvement can progress and require tracheostomy). There presently is no cure for LP, but some drugs (eg, oral dimethyl sulfoxide, etretinate, acitretin, penicillamine) and laser ablation/dermabrasion of papules are helpful in some cases.^1,7

To the Editor:

Epidermodysplasia verruciformis (EV) is a rare autosomal-recessive genodermatosis characterized by widespread infection with specific strains of human papillomavirus (HPV). Patients with EV have a unique susceptibility to acquire HPV due to defects in cellular immunity to the presenting antigens.¹ These defects may be related to mutations of the EVER genes or due to acquisition of an immunosuppressive condition.^2,3 Infections with HPV-3 and HPV-10 do not lead to the development of malignancies. However, infection with HPV-5, HPV-8, and HPV-14 can lead to the development of nonmelanoma skin cancers, usually squamous cell carcinomas (SCCs), in approximately 60% of patients.^3,4 This viral condition lasts throughout the patient’s lifetime and presents as tinea versicolor–like macules and patches. These lesions may be confused with seborrheic keratosis or verruca plana.⁵ Lesions typically are hypopigmented but occasionally may be hyperpigmented or erythematous. They often are found on the trunk, but lesions on the face, arms, palms, legs, and soles have been reported.⁵ Mucous membranes are always spared. Epidermodysplasia verruciformis often presents in childhood, except in cases related to acquired immunosuppression. The condition has no sex or racial predilection and no geographical preference.⁵

A 7-year-old boy (Fitzpatrick skin type V) presented with an asymptomatic rash on the trunk (Figure 1), dorsal aspect of the hands, and forehead. The lesions first appeared 5 years prior on the upper back and upper chest and had recently spread to the forehead and frontal aspect of the scalp. The patient had a history of myelomeningocele, which was corrected at birth with surgical placement of a ventriculoperitoneal shunt. The patient was otherwise healthy and met all appropriate developmental milestones for his age group. Family history revealed consanguinity of the patient’s paternal grandparents who were first cousins. The patient’s mother denied any other family member having similar rashes or lesions.

The patient had been treated for pityriasis versicolor on and off for 2 years by another dermatologist. His mother reported faithfully applying ketoconazole cream twice daily for several months with no improvement. She also reported using topical steroids, which did not provide any benefit. The patient and mother denied any associated pruritus, bleeding, burning, or physical discomfort.

Skin examination revealed diffuse, flat, polymorphous, hypopigmented and salmon-colored hyperkeratotic macules and patches with mild scaling on the upper region of the anterior aspect of the chest and upper back (Figure 2A). Additionally, the patient had an extensive number of lesions on the forehead and frontal aspect of the scalp (Figure 2B).

A shave biopsy demonstrated a thick basket weave stratum corneum, koilocytes, and large pale keratinocytes with characteristic blue cytoplasm. These findings were characteristic for EV.

At the patient’s 3-month follow-up visit, he again denied any symptoms associated with the lesions and reported that the appearance was diminishing in severity. On examination there was no evidence of SCC. The mother was advised to discontinue all topical treatments for the patient and return to the office every 3 to 6 months for regular skin surveillance. The mother was further advised to protect the patient from UV radiation with sunscreen and sun-protective clothing.

Epidermodysplasia verruciformis was first reported by Lewandowsky and Lutz⁶ in 1922. This rare condition often presents in childhood and is characterized by a persistent HPV infection and an autosomal-recessive inheritance pattern. Reports in the literature frequently involve kindreds. Often, patients with EV have a family history of first-degree or second-degree consanguinity.⁷

The clinical presentation of EV often resembles a pityriasis versicolor–like eruption. However, pityriasis versicolor is less commonly seen in childhood and is more prevalent in patients aged 21 to 30 years, likely due to increased sebum production and changing hormone levels. Furthermore, it is unusual to see pityriasis versicolor affect the face and scalp.⁸ Lesions of EV vary from hypopigmented and pinkish red macules to confluent patches and hyperkeratotic verrucalike lesions.³ Clinical characteristics also may include dyschromic patches; lesions that resemble flat warts on the trunk, face, and distal arms; and/or lesions that appear similar to seborrheic keratoses on the dorsal aspect of the hands.^9,10

Mutations of the EVER gene downregulate a cell’s ability to adequately attack the HPV antigens.¹¹ Although some patients with EV are found to have mutations of the EVER1 and EVER2 genes, a notable portion of patients with EV lack these mutations. Three other causes of EV include acquisition of immunosuppressive conditions including lymphoma, solid organ transplant, and human immunodeficiency virus. If one suspects autosomal-recessive inheritance of EV, genetic testing such as polymerase chain reaction DNA fragment analysis can be performed to determine if there are mutations on the EVER1 or EVER2 genes.¹²

The inability of patients with EV to mount an immune response to multiple types of HPV increases the risk for developing cutaneous malignancies.⁷ Additionally, it is known that UV radiation diminishes skin cell immunity, and the combination of EV and UV radiation further increases the risk for developing SCCs.¹¹ The development of nonmelanoma skin cancers usually occurs on sun-exposed skin 20 to 30 years after the onset of lesions, with the highest occurrence of SCCs presenting in the fourth decade of life.¹

Protection from UV light exposure is critical to reduce the risk for malignancy. Treatment options for EV lesions have included topical imiquimod 5%, 5-fluorouracil, oral isotretinoin, and intralesional interferon alfa, but patients are often refractory to these interventions. Curettage, surgical excision, electrosurgery, and laser ablation can be effective for individual lesions but carry a greater risk for scarring.¹ Photodynamic therapy with aminolevulinic acid and blue light represents a promising option that deserves further study.

Epidermodysplasia verruciformis should be considered as a differential diagnosis in all patients presenting with disseminated lesions resembling pityriasis versicolor that are unresponsive to treatment. A biopsy will help to establish the diagnosis. Patients should minimize sun exposure and report any skin lesions that are changing in appearance.

To the Editor:

Epidermodysplasia verruciformis (EV) is a rare autosomal-recessive genodermatosis characterized by widespread infection with specific strains of human papillomavirus (HPV). Patients with EV have a unique susceptibility to acquire HPV due to defects in cellular immunity to the presenting antigens.¹ These defects may be related to mutations of the EVER genes or due to acquisition of an immunosuppressive condition.^2,3 Infections with HPV-3 and HPV-10 do not lead to the development of malignancies. However, infection with HPV-5, HPV-8, and HPV-14 can lead to the development of nonmelanoma skin cancers, usually squamous cell carcinomas (SCCs), in approximately 60% of patients.^3,4 This viral condition lasts throughout the patient’s lifetime and presents as tinea versicolor–like macules and patches. These lesions may be confused with seborrheic keratosis or verruca plana.⁵ Lesions typically are hypopigmented but occasionally may be hyperpigmented or erythematous. They often are found on the trunk, but lesions on the face, arms, palms, legs, and soles have been reported.⁵ Mucous membranes are always spared. Epidermodysplasia verruciformis often presents in childhood, except in cases related to acquired immunosuppression. The condition has no sex or racial predilection and no geographical preference.⁵

A 7-year-old boy (Fitzpatrick skin type V) presented with an asymptomatic rash on the trunk (Figure 1), dorsal aspect of the hands, and forehead. The lesions first appeared 5 years prior on the upper back and upper chest and had recently spread to the forehead and frontal aspect of the scalp. The patient had a history of myelomeningocele, which was corrected at birth with surgical placement of a ventriculoperitoneal shunt. The patient was otherwise healthy and met all appropriate developmental milestones for his age group. Family history revealed consanguinity of the patient’s paternal grandparents who were first cousins. The patient’s mother denied any other family member having similar rashes or lesions.

The patient had been treated for pityriasis versicolor on and off for 2 years by another dermatologist. His mother reported faithfully applying ketoconazole cream twice daily for several months with no improvement. She also reported using topical steroids, which did not provide any benefit. The patient and mother denied any associated pruritus, bleeding, burning, or physical discomfort.

Skin examination revealed diffuse, flat, polymorphous, hypopigmented and salmon-colored hyperkeratotic macules and patches with mild scaling on the upper region of the anterior aspect of the chest and upper back (Figure 2A). Additionally, the patient had an extensive number of lesions on the forehead and frontal aspect of the scalp (Figure 2B).

A shave biopsy demonstrated a thick basket weave stratum corneum, koilocytes, and large pale keratinocytes with characteristic blue cytoplasm. These findings were characteristic for EV.

At the patient’s 3-month follow-up visit, he again denied any symptoms associated with the lesions and reported that the appearance was diminishing in severity. On examination there was no evidence of SCC. The mother was advised to discontinue all topical treatments for the patient and return to the office every 3 to 6 months for regular skin surveillance. The mother was further advised to protect the patient from UV radiation with sunscreen and sun-protective clothing.

Epidermodysplasia verruciformis was first reported by Lewandowsky and Lutz⁶ in 1922. This rare condition often presents in childhood and is characterized by a persistent HPV infection and an autosomal-recessive inheritance pattern. Reports in the literature frequently involve kindreds. Often, patients with EV have a family history of first-degree or second-degree consanguinity.⁷

The clinical presentation of EV often resembles a pityriasis versicolor–like eruption. However, pityriasis versicolor is less commonly seen in childhood and is more prevalent in patients aged 21 to 30 years, likely due to increased sebum production and changing hormone levels. Furthermore, it is unusual to see pityriasis versicolor affect the face and scalp.⁸ Lesions of EV vary from hypopigmented and pinkish red macules to confluent patches and hyperkeratotic verrucalike lesions.³ Clinical characteristics also may include dyschromic patches; lesions that resemble flat warts on the trunk, face, and distal arms; and/or lesions that appear similar to seborrheic keratoses on the dorsal aspect of the hands.^9,10

Mutations of the EVER gene downregulate a cell’s ability to adequately attack the HPV antigens.¹¹ Although some patients with EV are found to have mutations of the EVER1 and EVER2 genes, a notable portion of patients with EV lack these mutations. Three other causes of EV include acquisition of immunosuppressive conditions including lymphoma, solid organ transplant, and human immunodeficiency virus. If one suspects autosomal-recessive inheritance of EV, genetic testing such as polymerase chain reaction DNA fragment analysis can be performed to determine if there are mutations on the EVER1 or EVER2 genes.¹²

The inability of patients with EV to mount an immune response to multiple types of HPV increases the risk for developing cutaneous malignancies.⁷ Additionally, it is known that UV radiation diminishes skin cell immunity, and the combination of EV and UV radiation further increases the risk for developing SCCs.¹¹ The development of nonmelanoma skin cancers usually occurs on sun-exposed skin 20 to 30 years after the onset of lesions, with the highest occurrence of SCCs presenting in the fourth decade of life.¹

Protection from UV light exposure is critical to reduce the risk for malignancy. Treatment options for EV lesions have included topical imiquimod 5%, 5-fluorouracil, oral isotretinoin, and intralesional interferon alfa, but patients are often refractory to these interventions. Curettage, surgical excision, electrosurgery, and laser ablation can be effective for individual lesions but carry a greater risk for scarring.¹ Photodynamic therapy with aminolevulinic acid and blue light represents a promising option that deserves further study.

Epidermodysplasia verruciformis should be considered as a differential diagnosis in all patients presenting with disseminated lesions resembling pityriasis versicolor that are unresponsive to treatment. A biopsy will help to establish the diagnosis. Patients should minimize sun exposure and report any skin lesions that are changing in appearance.

To the Editor:

Epidermodysplasia verruciformis (EV) is a rare autosomal-recessive genodermatosis characterized by widespread infection with specific strains of human papillomavirus (HPV). Patients with EV have a unique susceptibility to acquire HPV due to defects in cellular immunity to the presenting antigens.¹ These defects may be related to mutations of the EVER genes or due to acquisition of an immunosuppressive condition.^2,3 Infections with HPV-3 and HPV-10 do not lead to the development of malignancies. However, infection with HPV-5, HPV-8, and HPV-14 can lead to the development of nonmelanoma skin cancers, usually squamous cell carcinomas (SCCs), in approximately 60% of patients.^3,4 This viral condition lasts throughout the patient’s lifetime and presents as tinea versicolor–like macules and patches. These lesions may be confused with seborrheic keratosis or verruca plana.⁵ Lesions typically are hypopigmented but occasionally may be hyperpigmented or erythematous. They often are found on the trunk, but lesions on the face, arms, palms, legs, and soles have been reported.⁵ Mucous membranes are always spared. Epidermodysplasia verruciformis often presents in childhood, except in cases related to acquired immunosuppression. The condition has no sex or racial predilection and no geographical preference.⁵

A 7-year-old boy (Fitzpatrick skin type V) presented with an asymptomatic rash on the trunk (Figure 1), dorsal aspect of the hands, and forehead. The lesions first appeared 5 years prior on the upper back and upper chest and had recently spread to the forehead and frontal aspect of the scalp. The patient had a history of myelomeningocele, which was corrected at birth with surgical placement of a ventriculoperitoneal shunt. The patient was otherwise healthy and met all appropriate developmental milestones for his age group. Family history revealed consanguinity of the patient’s paternal grandparents who were first cousins. The patient’s mother denied any other family member having similar rashes or lesions.

The patient had been treated for pityriasis versicolor on and off for 2 years by another dermatologist. His mother reported faithfully applying ketoconazole cream twice daily for several months with no improvement. She also reported using topical steroids, which did not provide any benefit. The patient and mother denied any associated pruritus, bleeding, burning, or physical discomfort.

Skin examination revealed diffuse, flat, polymorphous, hypopigmented and salmon-colored hyperkeratotic macules and patches with mild scaling on the upper region of the anterior aspect of the chest and upper back (Figure 2A). Additionally, the patient had an extensive number of lesions on the forehead and frontal aspect of the scalp (Figure 2B).

A shave biopsy demonstrated a thick basket weave stratum corneum, koilocytes, and large pale keratinocytes with characteristic blue cytoplasm. These findings were characteristic for EV.

At the patient’s 3-month follow-up visit, he again denied any symptoms associated with the lesions and reported that the appearance was diminishing in severity. On examination there was no evidence of SCC. The mother was advised to discontinue all topical treatments for the patient and return to the office every 3 to 6 months for regular skin surveillance. The mother was further advised to protect the patient from UV radiation with sunscreen and sun-protective clothing.

Epidermodysplasia verruciformis was first reported by Lewandowsky and Lutz⁶ in 1922. This rare condition often presents in childhood and is characterized by a persistent HPV infection and an autosomal-recessive inheritance pattern. Reports in the literature frequently involve kindreds. Often, patients with EV have a family history of first-degree or second-degree consanguinity.⁷

The clinical presentation of EV often resembles a pityriasis versicolor–like eruption. However, pityriasis versicolor is less commonly seen in childhood and is more prevalent in patients aged 21 to 30 years, likely due to increased sebum production and changing hormone levels. Furthermore, it is unusual to see pityriasis versicolor affect the face and scalp.⁸ Lesions of EV vary from hypopigmented and pinkish red macules to confluent patches and hyperkeratotic verrucalike lesions.³ Clinical characteristics also may include dyschromic patches; lesions that resemble flat warts on the trunk, face, and distal arms; and/or lesions that appear similar to seborrheic keratoses on the dorsal aspect of the hands.^9,10

Mutations of the EVER gene downregulate a cell’s ability to adequately attack the HPV antigens.¹¹ Although some patients with EV are found to have mutations of the EVER1 and EVER2 genes, a notable portion of patients with EV lack these mutations. Three other causes of EV include acquisition of immunosuppressive conditions including lymphoma, solid organ transplant, and human immunodeficiency virus. If one suspects autosomal-recessive inheritance of EV, genetic testing such as polymerase chain reaction DNA fragment analysis can be performed to determine if there are mutations on the EVER1 or EVER2 genes.¹²

The inability of patients with EV to mount an immune response to multiple types of HPV increases the risk for developing cutaneous malignancies.⁷ Additionally, it is known that UV radiation diminishes skin cell immunity, and the combination of EV and UV radiation further increases the risk for developing SCCs.¹¹ The development of nonmelanoma skin cancers usually occurs on sun-exposed skin 20 to 30 years after the onset of lesions, with the highest occurrence of SCCs presenting in the fourth decade of life.¹

Protection from UV light exposure is critical to reduce the risk for malignancy. Treatment options for EV lesions have included topical imiquimod 5%, 5-fluorouracil, oral isotretinoin, and intralesional interferon alfa, but patients are often refractory to these interventions. Curettage, surgical excision, electrosurgery, and laser ablation can be effective for individual lesions but carry a greater risk for scarring.¹ Photodynamic therapy with aminolevulinic acid and blue light represents a promising option that deserves further study.

Epidermodysplasia verruciformis should be considered as a differential diagnosis in all patients presenting with disseminated lesions resembling pityriasis versicolor that are unresponsive to treatment. A biopsy will help to establish the diagnosis. Patients should minimize sun exposure and report any skin lesions that are changing in appearance.

To the Editor:

Chondroid syringoma is a rare benign mixed tumor that originates from the sweat glands, typically presenting with both epithelial and mesenchymal components.¹ It differs from pleomorphic adenoma, which arises from salivary glands. The surgical approach for complete excision is different for the 2 tumors; therefore, definitive diagnosis is important. For chondroid syringoma, total excision is recommended,² while for pleomorphic adenoma, extracapsular dissection or superficial parotidectomy is commonly indicated. We report a case of a preauricular nodule at presentation and highlight the importance of differentiating a chondroid syringoma from a pleomorphic adenoma. This case is unique because of the anatomic location of the nodule, making diagnosis difficult because the tumor was abutting the parotid gland and a biopsy included normal salivary gland cells.

A 19-year-old man with a history of moderate acne on the shoulders, back, and face presented with a rapidly growing, painless nodule on right preauricular region of 6 months’ duration. The nodule was originally thought to be acne related and monitored, as the patient was asymptomatic. On examination the patient was found to have a firm, fixed, nontender, subcutaneous nodule overlying the right temporomandibular joint just anterior to the right tragus (Figure 1). Laboratory results were unremarkable. Computed tomography showed a subcutaneous nonaggressive-appearing soft-tissue mass measuring 16×17×12 mm just anterior and inferior to the external auditory canal cartilaginous segment with no bony abnormalities. The patient was initially treated with incomplete excision of the area for a presumed sebaceous cyst; 2 months later, an abnormal biopsy prompted a complete excisional biopsy.

Histologically, the initial incomplete excision biopsy revealed myxoid and chondroid tissue with glandular elements and adjacent lymph node with strong positivity for S-100 protein and moderate positivity for glial fibrillary acid protein, consistent with chondroid syringoma (Figure 2). Histological findings on second excision biopsy performed 2 months later showed tumor cells surrounded by normal salivary gland cells; therefore, it was difficult to define the origin of this tumor. Subsequent magnetic resonance imaging showed no evidence of the tumor and normal parotid gland borders.

Chondroid syringoma is a rare nonmelanoma skin tumor of the head and neck, mostly benign in nature but with malignant potential. Predominantly, it presents in males as an asymptomatic, slow-growing, nontender nodule.² Malignant chondroid syringomas are more rare, typically appear on the trunk and legs of females, and present as rapidly growing hard nodules. They can arise de novo or from a preexisting chondroid syringoma and can metastasize.^3,4

Clinically and histologically, chondroid syringoma resembles a pleomorphic adenoma. Its diagnosis is dependent on the clinical location to exclude origin in a salivary gland.⁵ Folliculosebaceous and myoepithelial differentiation within the tumor has been reported.⁶ Immunocytochemistry is the same in both types and is used to identify 2 prominent components—epithelial and mesenchymal—found in both chondroid syringoma and pleomorphic adenoma. Immunocytochemistry differentiates the epithelial component, which expresses cytokeratin, epithelial membrane antigen, and carcinoembryonic antigen. In contrast, the mesenchymal component expresses S-100, vimentin, and neuron‐specific enolase, and less often glial fibrillary acidic protein, smooth muscle actin, calponin, or p63.^5,7,8 Identification of both layers is a distinctive trait of both tumors, rendering it apart from other conditions in the differential diagnosis.⁵

Typical treatment options include excision, electrodesiccation, dermabrasion, and argon or CO₂ laser. Total excision is recommended if there is a benign tumor and complete excision is a cure.² One case of recurrent benign chondroid syringoma was treated by Mohs micrographic surgery on the eyebrow⁹; however, Mohs surgery was not recommended in our case due to concerns of spread if malignant as well as an unknown tumor depth, as these tumors have a tendency for deep infiltration.

Due to its anatomical location and presentation as an anterior preauricular mass, it was difficult to differentiate between chondroid syringoma from sweat gland origin and pleomorphic adenoma from the salivary gland. As seen in our case, it is important for physicians to be aware of the differential diagnosis for mixed tumors because it can have a notable effect on the type of surgical therapy and follow-up management.

To the Editor:

Chondroid syringoma is a rare benign mixed tumor that originates from the sweat glands, typically presenting with both epithelial and mesenchymal components.¹ It differs from pleomorphic adenoma, which arises from salivary glands. The surgical approach for complete excision is different for the 2 tumors; therefore, definitive diagnosis is important. For chondroid syringoma, total excision is recommended,² while for pleomorphic adenoma, extracapsular dissection or superficial parotidectomy is commonly indicated. We report a case of a preauricular nodule at presentation and highlight the importance of differentiating a chondroid syringoma from a pleomorphic adenoma. This case is unique because of the anatomic location of the nodule, making diagnosis difficult because the tumor was abutting the parotid gland and a biopsy included normal salivary gland cells.

A 19-year-old man with a history of moderate acne on the shoulders, back, and face presented with a rapidly growing, painless nodule on right preauricular region of 6 months’ duration. The nodule was originally thought to be acne related and monitored, as the patient was asymptomatic. On examination the patient was found to have a firm, fixed, nontender, subcutaneous nodule overlying the right temporomandibular joint just anterior to the right tragus (Figure 1). Laboratory results were unremarkable. Computed tomography showed a subcutaneous nonaggressive-appearing soft-tissue mass measuring 16×17×12 mm just anterior and inferior to the external auditory canal cartilaginous segment with no bony abnormalities. The patient was initially treated with incomplete excision of the area for a presumed sebaceous cyst; 2 months later, an abnormal biopsy prompted a complete excisional biopsy.

Histologically, the initial incomplete excision biopsy revealed myxoid and chondroid tissue with glandular elements and adjacent lymph node with strong positivity for S-100 protein and moderate positivity for glial fibrillary acid protein, consistent with chondroid syringoma (Figure 2). Histological findings on second excision biopsy performed 2 months later showed tumor cells surrounded by normal salivary gland cells; therefore, it was difficult to define the origin of this tumor. Subsequent magnetic resonance imaging showed no evidence of the tumor and normal parotid gland borders.

Chondroid syringoma is a rare nonmelanoma skin tumor of the head and neck, mostly benign in nature but with malignant potential. Predominantly, it presents in males as an asymptomatic, slow-growing, nontender nodule.² Malignant chondroid syringomas are more rare, typically appear on the trunk and legs of females, and present as rapidly growing hard nodules. They can arise de novo or from a preexisting chondroid syringoma and can metastasize.^3,4

Clinically and histologically, chondroid syringoma resembles a pleomorphic adenoma. Its diagnosis is dependent on the clinical location to exclude origin in a salivary gland.⁵ Folliculosebaceous and myoepithelial differentiation within the tumor has been reported.⁶ Immunocytochemistry is the same in both types and is used to identify 2 prominent components—epithelial and mesenchymal—found in both chondroid syringoma and pleomorphic adenoma. Immunocytochemistry differentiates the epithelial component, which expresses cytokeratin, epithelial membrane antigen, and carcinoembryonic antigen. In contrast, the mesenchymal component expresses S-100, vimentin, and neuron‐specific enolase, and less often glial fibrillary acidic protein, smooth muscle actin, calponin, or p63.^5,7,8 Identification of both layers is a distinctive trait of both tumors, rendering it apart from other conditions in the differential diagnosis.⁵

Typical treatment options include excision, electrodesiccation, dermabrasion, and argon or CO₂ laser. Total excision is recommended if there is a benign tumor and complete excision is a cure.² One case of recurrent benign chondroid syringoma was treated by Mohs micrographic surgery on the eyebrow⁹; however, Mohs surgery was not recommended in our case due to concerns of spread if malignant as well as an unknown tumor depth, as these tumors have a tendency for deep infiltration.

Due to its anatomical location and presentation as an anterior preauricular mass, it was difficult to differentiate between chondroid syringoma from sweat gland origin and pleomorphic adenoma from the salivary gland. As seen in our case, it is important for physicians to be aware of the differential diagnosis for mixed tumors because it can have a notable effect on the type of surgical therapy and follow-up management.

To the Editor:

Chondroid syringoma is a rare benign mixed tumor that originates from the sweat glands, typically presenting with both epithelial and mesenchymal components.¹ It differs from pleomorphic adenoma, which arises from salivary glands. The surgical approach for complete excision is different for the 2 tumors; therefore, definitive diagnosis is important. For chondroid syringoma, total excision is recommended,² while for pleomorphic adenoma, extracapsular dissection or superficial parotidectomy is commonly indicated. We report a case of a preauricular nodule at presentation and highlight the importance of differentiating a chondroid syringoma from a pleomorphic adenoma. This case is unique because of the anatomic location of the nodule, making diagnosis difficult because the tumor was abutting the parotid gland and a biopsy included normal salivary gland cells.

A 19-year-old man with a history of moderate acne on the shoulders, back, and face presented with a rapidly growing, painless nodule on right preauricular region of 6 months’ duration. The nodule was originally thought to be acne related and monitored, as the patient was asymptomatic. On examination the patient was found to have a firm, fixed, nontender, subcutaneous nodule overlying the right temporomandibular joint just anterior to the right tragus (Figure 1). Laboratory results were unremarkable. Computed tomography showed a subcutaneous nonaggressive-appearing soft-tissue mass measuring 16×17×12 mm just anterior and inferior to the external auditory canal cartilaginous segment with no bony abnormalities. The patient was initially treated with incomplete excision of the area for a presumed sebaceous cyst; 2 months later, an abnormal biopsy prompted a complete excisional biopsy.

Histologically, the initial incomplete excision biopsy revealed myxoid and chondroid tissue with glandular elements and adjacent lymph node with strong positivity for S-100 protein and moderate positivity for glial fibrillary acid protein, consistent with chondroid syringoma (Figure 2). Histological findings on second excision biopsy performed 2 months later showed tumor cells surrounded by normal salivary gland cells; therefore, it was difficult to define the origin of this tumor. Subsequent magnetic resonance imaging showed no evidence of the tumor and normal parotid gland borders.

Chondroid syringoma is a rare nonmelanoma skin tumor of the head and neck, mostly benign in nature but with malignant potential. Predominantly, it presents in males as an asymptomatic, slow-growing, nontender nodule.² Malignant chondroid syringomas are more rare, typically appear on the trunk and legs of females, and present as rapidly growing hard nodules. They can arise de novo or from a preexisting chondroid syringoma and can metastasize.^3,4

Clinically and histologically, chondroid syringoma resembles a pleomorphic adenoma. Its diagnosis is dependent on the clinical location to exclude origin in a salivary gland.⁵ Folliculosebaceous and myoepithelial differentiation within the tumor has been reported.⁶ Immunocytochemistry is the same in both types and is used to identify 2 prominent components—epithelial and mesenchymal—found in both chondroid syringoma and pleomorphic adenoma. Immunocytochemistry differentiates the epithelial component, which expresses cytokeratin, epithelial membrane antigen, and carcinoembryonic antigen. In contrast, the mesenchymal component expresses S-100, vimentin, and neuron‐specific enolase, and less often glial fibrillary acidic protein, smooth muscle actin, calponin, or p63.^5,7,8 Identification of both layers is a distinctive trait of both tumors, rendering it apart from other conditions in the differential diagnosis.⁵

Typical treatment options include excision, electrodesiccation, dermabrasion, and argon or CO₂ laser. Total excision is recommended if there is a benign tumor and complete excision is a cure.² One case of recurrent benign chondroid syringoma was treated by Mohs micrographic surgery on the eyebrow⁹; however, Mohs surgery was not recommended in our case due to concerns of spread if malignant as well as an unknown tumor depth, as these tumors have a tendency for deep infiltration.

Due to its anatomical location and presentation as an anterior preauricular mass, it was difficult to differentiate between chondroid syringoma from sweat gland origin and pleomorphic adenoma from the salivary gland. As seen in our case, it is important for physicians to be aware of the differential diagnosis for mixed tumors because it can have a notable effect on the type of surgical therapy and follow-up management.

Myth: UVB phototherapy causes skin cancer

Phototherapy is a common treatment modality for psoriasis patients that can be used in the physician’s office or psoriasis clinic or at home. Options include UVB phototherapy (broadband and narrowband), which slows the growth of affected skin cells; psoralen plus UVA (PUVA), which slows excessive skin cell growth; and excimer laser therapy, which targets select areas of the skin affected by mild to moderate psoriasis and is particularly useful for scalp psoriasis. Each of these therapies may be combined with other topical and/or systemic psoriasis treatments. The effects of UV light on the skin and the connection to skin cancer is widely known. Therefore, patient education on the risk for skin cancer with phototherapy is essential.

Evidence suggests that UVB phototherapy remains a safe treatment modality. In a 2005 analysis of prospective and retrospective studies on skin cancer risk from UVB phototherapy, 11 studies (10 concerning psoriasis patients) were reviewed and the researchers concluded that all studies eventually showed no increased skin cancer risk with UVB phototherapy. One of the PUVA cohort studies examined genital skin cancers and found an increased rate of genital tumors associated with UVB phototherapy.

Another analysis to define the long-term carcinogenic risk for narrowband UVB treatment found that there was no association between narrowband UVB exposure alone (without PUVA) and any skin cancer. For patients treated with narrowband UVB and PUVA, there was a small increase in basal cell carcinomas.

Dermatologists should monitor psoriasis patients for self-administered treatment with tanning beds. Based on a questionnaire sent to approximately 14,000 subscribers of National Psoriasis Foundation emails, 62% of 617 tanners started tanning to treat psoriasis; they were more likely to have received medical phototherapy and had more severe psoriasis. Approximately 30% of these patients indicated that they used tanning as a self-treatment for psoriasis because of the inconvenience and cost of UV light treatment in a physician’s office as well as treatment failure of other therapies prescribed by the physician. “Our results imply that tanning bed usage among psoriasis sufferers is widespread and linked with tanning addiction,” reported Felton et al. “Practitioners should be particularly vigilant to the possibility of tanning bed usage in at-risk patients.” These patients may be at increased risk for skin cancer. Problematic tanning behaviors may be seen in younger female patients diagnosed with psoriasis at an early age as well as patients with severe psoriasis who were previously prescribed phototherapy treatment.

Expert Commentary on next page

Expert Commentary

UVB phototherapy is an effective therapy that does not increase the risk of nonmelanoma skin cancers (NMSCs), according to the 2 analyses mentioned above. When I discuss the risks and benefits of UVB phototherapy with psoriasis patients, I do say that there is a theoretical increased risk for NMSC but that the 2005 study mentioned above does not indicate an increased risk. However, UVB phototherapy and cyclosporine should not be combined, as this combination does increase the risk for NMSC.

Psoralen plus UVA definitely will increase the risk for NMSC, particularly squamous cell carcinoma. However, in this age of the biologics, PUVA use has fallen out of favor, partly due to the increased risk for NMSC, and many patients will not encounter dermatology practices that still use PUVA.
—Jashin J. Wu, MD (Los Angeles, California)

Myth: UVB phototherapy causes skin cancer

Phototherapy is a common treatment modality for psoriasis patients that can be used in the physician’s office or psoriasis clinic or at home. Options include UVB phototherapy (broadband and narrowband), which slows the growth of affected skin cells; psoralen plus UVA (PUVA), which slows excessive skin cell growth; and excimer laser therapy, which targets select areas of the skin affected by mild to moderate psoriasis and is particularly useful for scalp psoriasis. Each of these therapies may be combined with other topical and/or systemic psoriasis treatments. The effects of UV light on the skin and the connection to skin cancer is widely known. Therefore, patient education on the risk for skin cancer with phototherapy is essential.

Evidence suggests that UVB phototherapy remains a safe treatment modality. In a 2005 analysis of prospective and retrospective studies on skin cancer risk from UVB phototherapy, 11 studies (10 concerning psoriasis patients) were reviewed and the researchers concluded that all studies eventually showed no increased skin cancer risk with UVB phototherapy. One of the PUVA cohort studies examined genital skin cancers and found an increased rate of genital tumors associated with UVB phototherapy.

Another analysis to define the long-term carcinogenic risk for narrowband UVB treatment found that there was no association between narrowband UVB exposure alone (without PUVA) and any skin cancer. For patients treated with narrowband UVB and PUVA, there was a small increase in basal cell carcinomas.

Dermatologists should monitor psoriasis patients for self-administered treatment with tanning beds. Based on a questionnaire sent to approximately 14,000 subscribers of National Psoriasis Foundation emails, 62% of 617 tanners started tanning to treat psoriasis; they were more likely to have received medical phototherapy and had more severe psoriasis. Approximately 30% of these patients indicated that they used tanning as a self-treatment for psoriasis because of the inconvenience and cost of UV light treatment in a physician’s office as well as treatment failure of other therapies prescribed by the physician. “Our results imply that tanning bed usage among psoriasis sufferers is widespread and linked with tanning addiction,” reported Felton et al. “Practitioners should be particularly vigilant to the possibility of tanning bed usage in at-risk patients.” These patients may be at increased risk for skin cancer. Problematic tanning behaviors may be seen in younger female patients diagnosed with psoriasis at an early age as well as patients with severe psoriasis who were previously prescribed phototherapy treatment.

Expert Commentary on next page

Expert Commentary

UVB phototherapy is an effective therapy that does not increase the risk of nonmelanoma skin cancers (NMSCs), according to the 2 analyses mentioned above. When I discuss the risks and benefits of UVB phototherapy with psoriasis patients, I do say that there is a theoretical increased risk for NMSC but that the 2005 study mentioned above does not indicate an increased risk. However, UVB phototherapy and cyclosporine should not be combined, as this combination does increase the risk for NMSC.

Psoralen plus UVA definitely will increase the risk for NMSC, particularly squamous cell carcinoma. However, in this age of the biologics, PUVA use has fallen out of favor, partly due to the increased risk for NMSC, and many patients will not encounter dermatology practices that still use PUVA.
—Jashin J. Wu, MD (Los Angeles, California)

Myth: UVB phototherapy causes skin cancer

Phototherapy is a common treatment modality for psoriasis patients that can be used in the physician’s office or psoriasis clinic or at home. Options include UVB phototherapy (broadband and narrowband), which slows the growth of affected skin cells; psoralen plus UVA (PUVA), which slows excessive skin cell growth; and excimer laser therapy, which targets select areas of the skin affected by mild to moderate psoriasis and is particularly useful for scalp psoriasis. Each of these therapies may be combined with other topical and/or systemic psoriasis treatments. The effects of UV light on the skin and the connection to skin cancer is widely known. Therefore, patient education on the risk for skin cancer with phototherapy is essential.

Evidence suggests that UVB phototherapy remains a safe treatment modality. In a 2005 analysis of prospective and retrospective studies on skin cancer risk from UVB phototherapy, 11 studies (10 concerning psoriasis patients) were reviewed and the researchers concluded that all studies eventually showed no increased skin cancer risk with UVB phototherapy. One of the PUVA cohort studies examined genital skin cancers and found an increased rate of genital tumors associated with UVB phototherapy.

Another analysis to define the long-term carcinogenic risk for narrowband UVB treatment found that there was no association between narrowband UVB exposure alone (without PUVA) and any skin cancer. For patients treated with narrowband UVB and PUVA, there was a small increase in basal cell carcinomas.

Dermatologists should monitor psoriasis patients for self-administered treatment with tanning beds. Based on a questionnaire sent to approximately 14,000 subscribers of National Psoriasis Foundation emails, 62% of 617 tanners started tanning to treat psoriasis; they were more likely to have received medical phototherapy and had more severe psoriasis. Approximately 30% of these patients indicated that they used tanning as a self-treatment for psoriasis because of the inconvenience and cost of UV light treatment in a physician’s office as well as treatment failure of other therapies prescribed by the physician. “Our results imply that tanning bed usage among psoriasis sufferers is widespread and linked with tanning addiction,” reported Felton et al. “Practitioners should be particularly vigilant to the possibility of tanning bed usage in at-risk patients.” These patients may be at increased risk for skin cancer. Problematic tanning behaviors may be seen in younger female patients diagnosed with psoriasis at an early age as well as patients with severe psoriasis who were previously prescribed phototherapy treatment.

Expert Commentary on next page

Expert Commentary

UVB phototherapy is an effective therapy that does not increase the risk of nonmelanoma skin cancers (NMSCs), according to the 2 analyses mentioned above. When I discuss the risks and benefits of UVB phototherapy with psoriasis patients, I do say that there is a theoretical increased risk for NMSC but that the 2005 study mentioned above does not indicate an increased risk. However, UVB phototherapy and cyclosporine should not be combined, as this combination does increase the risk for NMSC.

Psoralen plus UVA definitely will increase the risk for NMSC, particularly squamous cell carcinoma. However, in this age of the biologics, PUVA use has fallen out of favor, partly due to the increased risk for NMSC, and many patients will not encounter dermatology practices that still use PUVA.
—Jashin J. Wu, MD (Los Angeles, California)