Cutis

To the Editor:

Albendazole is a commonly prescribed anthelmintic that typically is well tolerated. Its broadest application is in developing countries that have a high rate of endemic nematode infection.^1,2 Albendazole belongs to the benzimidazole class of anthelmintic chemotherapeutic agents that function by inhibiting microtubule dynamics, resulting in cytotoxic antimitotic effects.³ Benzimidazoles (eg, albendazole, mebendazole) have a binding affinity for helminthic β-tubulin that is 25- to 400-times greater than their binding affinity for the mammalian counterpart.⁴ Consequently, benzimidazoles generally are afforded a very broad therapeutic index for helminthic infection.

A 53-year-old man presented to the emergency department (ED) after an episode of syncope and sudden hair loss. At presentation he had a fever (temperature, 103 °F [39.4 °C]), a heart rate of 120 bpm, and pancytopenia (white blood cell count, 0.4×10³/μL [reference range, 4.0–10.0×10³/μL]; hemoglobin, 7.0 g/dL [reference range, 11.2–15.7 g/dL]; platelet count, 100×10³/μL [reference range, 150–400×10³/μL]). A toxicology screen was positive for cocaine, opiates, and benzodiazepines. The blood alcohol concentration was 126 mg/dL.

The patient reported severe gastrointestinal (GI) distress and diarrhea for the last year as well as a 25-lb weight loss. He discussed his belief that his GI symptoms were due to a parasite he had acquired the year prior; however, he reported that an exhaustive outpatient GI workup had been negative. Two weeks before presentation to our ED, the patient presented to another ED with stomach upset and was given a dose of albendazole. Perceiving alleviation of his symptoms, he purchased 2 bottles of veterinary albendazole online and consumed 113,000 mg—approximately 300 times the standard dose of 400 mg.

A dermatologic examination in our ED demonstrated reticulated violaceous patches on the face and severe alopecia with preferential sparing of the occipital scalp (Figure 1). Photographs taken by the patient on his phone from a week prior to presentation showed no facial dyschromia or signs of hair loss. A punch biopsy of the chin demonstrated perivascular and perifollicular dermatitis with eosinophils, most consistent with a drug reaction.

To the Editor:

Albendazole is a commonly prescribed anthelmintic that typically is well tolerated. Its broadest application is in developing countries that have a high rate of endemic nematode infection.^1,2 Albendazole belongs to the benzimidazole class of anthelmintic chemotherapeutic agents that function by inhibiting microtubule dynamics, resulting in cytotoxic antimitotic effects.³ Benzimidazoles (eg, albendazole, mebendazole) have a binding affinity for helminthic β-tubulin that is 25- to 400-times greater than their binding affinity for the mammalian counterpart.⁴ Consequently, benzimidazoles generally are afforded a very broad therapeutic index for helminthic infection.

A 53-year-old man presented to the emergency department (ED) after an episode of syncope and sudden hair loss. At presentation he had a fever (temperature, 103 °F [39.4 °C]), a heart rate of 120 bpm, and pancytopenia (white blood cell count, 0.4×10³/μL [reference range, 4.0–10.0×10³/μL]; hemoglobin, 7.0 g/dL [reference range, 11.2–15.7 g/dL]; platelet count, 100×10³/μL [reference range, 150–400×10³/μL]). A toxicology screen was positive for cocaine, opiates, and benzodiazepines. The blood alcohol concentration was 126 mg/dL.

The patient reported severe gastrointestinal (GI) distress and diarrhea for the last year as well as a 25-lb weight loss. He discussed his belief that his GI symptoms were due to a parasite he had acquired the year prior; however, he reported that an exhaustive outpatient GI workup had been negative. Two weeks before presentation to our ED, the patient presented to another ED with stomach upset and was given a dose of albendazole. Perceiving alleviation of his symptoms, he purchased 2 bottles of veterinary albendazole online and consumed 113,000 mg—approximately 300 times the standard dose of 400 mg.

A dermatologic examination in our ED demonstrated reticulated violaceous patches on the face and severe alopecia with preferential sparing of the occipital scalp (Figure 1). Photographs taken by the patient on his phone from a week prior to presentation showed no facial dyschromia or signs of hair loss. A punch biopsy of the chin demonstrated perivascular and perifollicular dermatitis with eosinophils, most consistent with a drug reaction.

To the Editor:

Albendazole is a commonly prescribed anthelmintic that typically is well tolerated. Its broadest application is in developing countries that have a high rate of endemic nematode infection.^1,2 Albendazole belongs to the benzimidazole class of anthelmintic chemotherapeutic agents that function by inhibiting microtubule dynamics, resulting in cytotoxic antimitotic effects.³ Benzimidazoles (eg, albendazole, mebendazole) have a binding affinity for helminthic β-tubulin that is 25- to 400-times greater than their binding affinity for the mammalian counterpart.⁴ Consequently, benzimidazoles generally are afforded a very broad therapeutic index for helminthic infection.

A 53-year-old man presented to the emergency department (ED) after an episode of syncope and sudden hair loss. At presentation he had a fever (temperature, 103 °F [39.4 °C]), a heart rate of 120 bpm, and pancytopenia (white blood cell count, 0.4×10³/μL [reference range, 4.0–10.0×10³/μL]; hemoglobin, 7.0 g/dL [reference range, 11.2–15.7 g/dL]; platelet count, 100×10³/μL [reference range, 150–400×10³/μL]). A toxicology screen was positive for cocaine, opiates, and benzodiazepines. The blood alcohol concentration was 126 mg/dL.

The patient reported severe gastrointestinal (GI) distress and diarrhea for the last year as well as a 25-lb weight loss. He discussed his belief that his GI symptoms were due to a parasite he had acquired the year prior; however, he reported that an exhaustive outpatient GI workup had been negative. Two weeks before presentation to our ED, the patient presented to another ED with stomach upset and was given a dose of albendazole. Perceiving alleviation of his symptoms, he purchased 2 bottles of veterinary albendazole online and consumed 113,000 mg—approximately 300 times the standard dose of 400 mg.

A dermatologic examination in our ED demonstrated reticulated violaceous patches on the face and severe alopecia with preferential sparing of the occipital scalp (Figure 1). Photographs taken by the patient on his phone from a week prior to presentation showed no facial dyschromia or signs of hair loss. A punch biopsy of the chin demonstrated perivascular and perifollicular dermatitis with eosinophils, most consistent with a drug reaction.

To the Editor:

A 59-year-old man was referred to our clinic for a rash, fever, and night sweats following treatment for metastatic seminoma with cisplatin and etoposide. Physical examination revealed indurated erythematous papules and plaques on the trunk and upper and lower extremities, some with annular or arcuate configuration with trailing scale (Figure, A). A skin biopsy demonstrated mild papillary dermal edema with a mixed infiltrate of mononuclear cells, neutrophils, eosinophils, mast cells, lymphocytes, and karyorrhectic debris without evidence of leukocytoclastic vasculitis. The histopathologic differential diagnosis included a histiocytoid variant of Sweet syndrome (SS), and our patient’s rapid clinical response to corticosteroids supported this diagnosis.

With a relapsing and remitting course over 3 years, the rash eventually evolved into more edematous papules and plaques (Figure, B), and a repeat biopsy 3 years later was consistent with classic SS. Although the patient's condition improved with prednisone, attempts to taper prednisone invariably resulted in relapse. Multiple steroid-sparing agents were trialed over the course of 3 years including dapsone and mycophenolate mofetil, both of which resulted in hypersensitivity drug eruptions. Colchicine and methotrexate were ineffective. Thalidomide strongly was considered but ultimately was avoided due to substantial existing neuropathy associated with his prior chemotherapy for metastatic seminoma.

Four years after the initial diagnosis of SS, our patient presented with dyspnea and weight loss. Computed tomography revealed a nearly confluent miliary pattern of nodularity in the lungs. A wedge biopsy demonstrated pneumonitis with intra-alveolar fibrin and neutrophils with a notable absence of granulomatous inflammation. Fungal and acid-fast bacilli staining as well as tissue cultures were negative. He had a history of Mycobacterium kansasii pulmonary infection treated 18 months prior; however, in this instance, the histopathology, negative microbial cultures, and rapid steroid responsiveness were consistent with pulmonary involvement of SS. Over the ensuing 2 years, the patient developed worsening of his chronic anemia. He was diagnosed with myelodysplastic syndrome (MDS) by bone marrow biopsy, despite having a normal bone marrow biopsy more than 3 years prior to evaluate his anemia. At this time, thalidomide was initiated at 50 mg daily leading to notable improvement in his SS symptoms; however, he developed worsening neuropathy resulting in the discontinuation of this treatment 2 months later. An investigational combination of vosaroxin and azacytidine was used to treat his MDS, resulting in normalization of blood counts and remission from SS.

Sweet syndrome may occur in the setting of undiagnosed cancer or may signal the return of a previously treated malignancy. The first description of SS associated with solid tumors was in a patient with testicular cancer,¹ which prompted continuous surveillance for recurrent seminoma in our patient, though none was found. Hematologic malignancies, as well as MDS, often are associated with SS.² In our patient, multiple atypical features linked the development of SS to the ultimate presentation of MDS. The initial finding of a histiocytoid variant has been described in a case series of 9 patients with chronic relapsing SS who eventually developed MDS with latency of up to 7 years. The histopathology in these cases evolved over time to that of classic neutrophilic SS.³ Pulmonary involvement of SS is another interesting aspect of our case. In one analysis, 18 of 34 (53%) cases with pulmonary involvement featured hematologic pathology, including myelodysplasia and acute leukemia.⁴

In our patient, SS preceded the clinical manifestation of MDS by 6 years. A similar phenomenon has been described in a patient with SS that preceded myelodysplasia by 30 months and was recalcitrant to numerous steroid-sparing therapies except thalidomide, despite the persistence of myelodysplasia. Tapering thalidomide, however, resulted in recurrence of SS lesions in that patient.⁵ In another case, resolution of myelodysplasia from azacytidine treatment was associated with remission from SS.⁶

Our case represents a confluence of atypical features that seem to define myelodysplasia-associated SS, including the initial presentation with a clinically atypical histiocytoid variant, chronic relapsing and remitting course, and extracutaneous involvement of the lungs. These findings should prompt surveillance for hematologic malignancy or myelodysplasia. Serial bone marrow biopsies were required to evaluate persistent anemia before the histopathologic findings of MDS became apparent in our patient. Thalidomide was an effective treatment for the cutaneous manifestations in our patient and should be considered as a steroid-sparing agent in the treatment of recalcitrant SS. Despite the discontinuation of thalidomide therapy, effective control of our patient’s myelodysplasia with chemotherapy has kept him in remission from SS for more than 7 years of follow-up, suggesting a causal relationship between these disorders.

To the Editor:

A 59-year-old man was referred to our clinic for a rash, fever, and night sweats following treatment for metastatic seminoma with cisplatin and etoposide. Physical examination revealed indurated erythematous papules and plaques on the trunk and upper and lower extremities, some with annular or arcuate configuration with trailing scale (Figure, A). A skin biopsy demonstrated mild papillary dermal edema with a mixed infiltrate of mononuclear cells, neutrophils, eosinophils, mast cells, lymphocytes, and karyorrhectic debris without evidence of leukocytoclastic vasculitis. The histopathologic differential diagnosis included a histiocytoid variant of Sweet syndrome (SS), and our patient’s rapid clinical response to corticosteroids supported this diagnosis.

With a relapsing and remitting course over 3 years, the rash eventually evolved into more edematous papules and plaques (Figure, B), and a repeat biopsy 3 years later was consistent with classic SS. Although the patient's condition improved with prednisone, attempts to taper prednisone invariably resulted in relapse. Multiple steroid-sparing agents were trialed over the course of 3 years including dapsone and mycophenolate mofetil, both of which resulted in hypersensitivity drug eruptions. Colchicine and methotrexate were ineffective. Thalidomide strongly was considered but ultimately was avoided due to substantial existing neuropathy associated with his prior chemotherapy for metastatic seminoma.

Four years after the initial diagnosis of SS, our patient presented with dyspnea and weight loss. Computed tomography revealed a nearly confluent miliary pattern of nodularity in the lungs. A wedge biopsy demonstrated pneumonitis with intra-alveolar fibrin and neutrophils with a notable absence of granulomatous inflammation. Fungal and acid-fast bacilli staining as well as tissue cultures were negative. He had a history of Mycobacterium kansasii pulmonary infection treated 18 months prior; however, in this instance, the histopathology, negative microbial cultures, and rapid steroid responsiveness were consistent with pulmonary involvement of SS. Over the ensuing 2 years, the patient developed worsening of his chronic anemia. He was diagnosed with myelodysplastic syndrome (MDS) by bone marrow biopsy, despite having a normal bone marrow biopsy more than 3 years prior to evaluate his anemia. At this time, thalidomide was initiated at 50 mg daily leading to notable improvement in his SS symptoms; however, he developed worsening neuropathy resulting in the discontinuation of this treatment 2 months later. An investigational combination of vosaroxin and azacytidine was used to treat his MDS, resulting in normalization of blood counts and remission from SS.

Sweet syndrome may occur in the setting of undiagnosed cancer or may signal the return of a previously treated malignancy. The first description of SS associated with solid tumors was in a patient with testicular cancer,¹ which prompted continuous surveillance for recurrent seminoma in our patient, though none was found. Hematologic malignancies, as well as MDS, often are associated with SS.² In our patient, multiple atypical features linked the development of SS to the ultimate presentation of MDS. The initial finding of a histiocytoid variant has been described in a case series of 9 patients with chronic relapsing SS who eventually developed MDS with latency of up to 7 years. The histopathology in these cases evolved over time to that of classic neutrophilic SS.³ Pulmonary involvement of SS is another interesting aspect of our case. In one analysis, 18 of 34 (53%) cases with pulmonary involvement featured hematologic pathology, including myelodysplasia and acute leukemia.⁴

In our patient, SS preceded the clinical manifestation of MDS by 6 years. A similar phenomenon has been described in a patient with SS that preceded myelodysplasia by 30 months and was recalcitrant to numerous steroid-sparing therapies except thalidomide, despite the persistence of myelodysplasia. Tapering thalidomide, however, resulted in recurrence of SS lesions in that patient.⁵ In another case, resolution of myelodysplasia from azacytidine treatment was associated with remission from SS.⁶

Our case represents a confluence of atypical features that seem to define myelodysplasia-associated SS, including the initial presentation with a clinically atypical histiocytoid variant, chronic relapsing and remitting course, and extracutaneous involvement of the lungs. These findings should prompt surveillance for hematologic malignancy or myelodysplasia. Serial bone marrow biopsies were required to evaluate persistent anemia before the histopathologic findings of MDS became apparent in our patient. Thalidomide was an effective treatment for the cutaneous manifestations in our patient and should be considered as a steroid-sparing agent in the treatment of recalcitrant SS. Despite the discontinuation of thalidomide therapy, effective control of our patient’s myelodysplasia with chemotherapy has kept him in remission from SS for more than 7 years of follow-up, suggesting a causal relationship between these disorders.

To the Editor:

A 59-year-old man was referred to our clinic for a rash, fever, and night sweats following treatment for metastatic seminoma with cisplatin and etoposide. Physical examination revealed indurated erythematous papules and plaques on the trunk and upper and lower extremities, some with annular or arcuate configuration with trailing scale (Figure, A). A skin biopsy demonstrated mild papillary dermal edema with a mixed infiltrate of mononuclear cells, neutrophils, eosinophils, mast cells, lymphocytes, and karyorrhectic debris without evidence of leukocytoclastic vasculitis. The histopathologic differential diagnosis included a histiocytoid variant of Sweet syndrome (SS), and our patient’s rapid clinical response to corticosteroids supported this diagnosis.

With a relapsing and remitting course over 3 years, the rash eventually evolved into more edematous papules and plaques (Figure, B), and a repeat biopsy 3 years later was consistent with classic SS. Although the patient's condition improved with prednisone, attempts to taper prednisone invariably resulted in relapse. Multiple steroid-sparing agents were trialed over the course of 3 years including dapsone and mycophenolate mofetil, both of which resulted in hypersensitivity drug eruptions. Colchicine and methotrexate were ineffective. Thalidomide strongly was considered but ultimately was avoided due to substantial existing neuropathy associated with his prior chemotherapy for metastatic seminoma.

Four years after the initial diagnosis of SS, our patient presented with dyspnea and weight loss. Computed tomography revealed a nearly confluent miliary pattern of nodularity in the lungs. A wedge biopsy demonstrated pneumonitis with intra-alveolar fibrin and neutrophils with a notable absence of granulomatous inflammation. Fungal and acid-fast bacilli staining as well as tissue cultures were negative. He had a history of Mycobacterium kansasii pulmonary infection treated 18 months prior; however, in this instance, the histopathology, negative microbial cultures, and rapid steroid responsiveness were consistent with pulmonary involvement of SS. Over the ensuing 2 years, the patient developed worsening of his chronic anemia. He was diagnosed with myelodysplastic syndrome (MDS) by bone marrow biopsy, despite having a normal bone marrow biopsy more than 3 years prior to evaluate his anemia. At this time, thalidomide was initiated at 50 mg daily leading to notable improvement in his SS symptoms; however, he developed worsening neuropathy resulting in the discontinuation of this treatment 2 months later. An investigational combination of vosaroxin and azacytidine was used to treat his MDS, resulting in normalization of blood counts and remission from SS.

Sweet syndrome may occur in the setting of undiagnosed cancer or may signal the return of a previously treated malignancy. The first description of SS associated with solid tumors was in a patient with testicular cancer,¹ which prompted continuous surveillance for recurrent seminoma in our patient, though none was found. Hematologic malignancies, as well as MDS, often are associated with SS.² In our patient, multiple atypical features linked the development of SS to the ultimate presentation of MDS. The initial finding of a histiocytoid variant has been described in a case series of 9 patients with chronic relapsing SS who eventually developed MDS with latency of up to 7 years. The histopathology in these cases evolved over time to that of classic neutrophilic SS.³ Pulmonary involvement of SS is another interesting aspect of our case. In one analysis, 18 of 34 (53%) cases with pulmonary involvement featured hematologic pathology, including myelodysplasia and acute leukemia.⁴

In our patient, SS preceded the clinical manifestation of MDS by 6 years. A similar phenomenon has been described in a patient with SS that preceded myelodysplasia by 30 months and was recalcitrant to numerous steroid-sparing therapies except thalidomide, despite the persistence of myelodysplasia. Tapering thalidomide, however, resulted in recurrence of SS lesions in that patient.⁵ In another case, resolution of myelodysplasia from azacytidine treatment was associated with remission from SS.⁶

Our case represents a confluence of atypical features that seem to define myelodysplasia-associated SS, including the initial presentation with a clinically atypical histiocytoid variant, chronic relapsing and remitting course, and extracutaneous involvement of the lungs. These findings should prompt surveillance for hematologic malignancy or myelodysplasia. Serial bone marrow biopsies were required to evaluate persistent anemia before the histopathologic findings of MDS became apparent in our patient. Thalidomide was an effective treatment for the cutaneous manifestations in our patient and should be considered as a steroid-sparing agent in the treatment of recalcitrant SS. Despite the discontinuation of thalidomide therapy, effective control of our patient’s myelodysplasia with chemotherapy has kept him in remission from SS for more than 7 years of follow-up, suggesting a causal relationship between these disorders.

To the Editor:

An otherwise healthy 26-year-old man presented to our outpatient clinic with a 15- to 20-mm, shiny, friable-appearing, red umbilical nodule with clear malodorous discharge (Figure 1). The lesion developed 2 weeks prior and gradually increased in size and discomfort. The patient reported mild associated abdominal pain. He had no fever, changes in urination or bowel movements, or prior history of umbilical growths or drainage. The abdomen was tender to palpation.

Differential diagnoses included pyogenic granuloma, umbilical hernia, epidermoid cyst or abscess, and malignancy (low suspicion). A biopsy was not performed due to concern for bleeding or communication with the bowel. A complete blood cell count, comprehensive metabolic panel, and urinalysis were unremarkable except for mild leukocytosis and elevated C-reactive protein. Ultrasonography revealed a 1.4×1.3-cm inflammatory umbilical mass with no communication with the bowel. The patient was referred to the emergency department (ED) for further evaluation. Computed tomography (CT) revealed periumbilical inflammation and an associated 1-cm calcification that appeared to be connected to a potential tract from the bladder, suggestive of a urachal remnant calcification (Figure 2). The patient was diagnosed with a persistent urachal remnant, discharged home with ciprofloxacin, and scheduled for a follow-up with urology.

The patient returned to the ED 3 days later with painful umbilical bleeding (Figure 3). While there, the patient extracted a 1-cm stone from the lesion, consistent with the calcification visualized on CT scan. Computed tomographic virtual cystoscopy showed no connection between the bladder and umbilicus. He was diagnosed with an umbilical-urachal sinus. Complete surgical excision was recommended and performed by urology without complication.

We report an unusual presentation of a symptomatic urachal remnant in an adult. During embryogenesis, the urachus connects the umbilicus to the developing bladder and normally involutes during development. Incomplete regression can cause rare pathological urachal anomalies. The clinical presentation is nonspecific and differs between children and adults, with most cases presenting during infancy or childhood.¹ Pediatric urachal abnormalities often present with umbilical drainage, abdominal pain, a palpable mass, an abnormal appearance of the umbilicus, or urinary tract infections.^2,3 In adults, the most common symptoms include hematuria, pain, or dysuria. Alternatively, they may be asympomatic³ or present with periumbilical dermatitis⁴ or abscess. Rodrigues and Gandhi⁵ reported another case of a symptomatic calculus formed within a urachal remnant. Calcifications in urachal remnants are rare and usually are reported as incidental radiologic findings.

Overall, visible umbilical masses occur infrequently. In addition to urachal anomalies, the differential diagnosis includes several benign and malignant pathologies. Benign causes include epidermoid cysts, foreign body granulomas, pyogenic granulomas, abscesses, hamartomas, nevi, hemangiomas, dermatofibromas, neurofibromas, lipomas, granular cell tumors, desmoid tumors, keloid scars, omphaliths, hernias, or omphalomesenteric duct remnants.⁶ Primary malignancies (eg, skin cancers, urachal adenocarcinoma, mesenchymal tumors) or metastasis (ie, Sister Mary Joseph nodule) also can present as umbilical nodules.

The wide range of clinical presentations of urachal anomalies combined with the rarity make diagnosis difficult. Thus, it is essential to have a high index of suspicion and awareness of how they can present. Ultrasonography and CT scan are useful tools in making the diagnosis. Urachal anomalies are prone to infection or can be associated with malignancy; therefore, timely and correct diagnosis is critical. Although surgical removal is the primary treatment for urachal anomalies, it may not be the primary treatment of the other entities included in the differential diagnosis of umbilical nodules. For example, the Sister Mary Joseph nodule can be associated with various primary malignancies, which should be treated accordingly.

To the Editor:

An otherwise healthy 26-year-old man presented to our outpatient clinic with a 15- to 20-mm, shiny, friable-appearing, red umbilical nodule with clear malodorous discharge (Figure 1). The lesion developed 2 weeks prior and gradually increased in size and discomfort. The patient reported mild associated abdominal pain. He had no fever, changes in urination or bowel movements, or prior history of umbilical growths or drainage. The abdomen was tender to palpation.

Differential diagnoses included pyogenic granuloma, umbilical hernia, epidermoid cyst or abscess, and malignancy (low suspicion). A biopsy was not performed due to concern for bleeding or communication with the bowel. A complete blood cell count, comprehensive metabolic panel, and urinalysis were unremarkable except for mild leukocytosis and elevated C-reactive protein. Ultrasonography revealed a 1.4×1.3-cm inflammatory umbilical mass with no communication with the bowel. The patient was referred to the emergency department (ED) for further evaluation. Computed tomography (CT) revealed periumbilical inflammation and an associated 1-cm calcification that appeared to be connected to a potential tract from the bladder, suggestive of a urachal remnant calcification (Figure 2). The patient was diagnosed with a persistent urachal remnant, discharged home with ciprofloxacin, and scheduled for a follow-up with urology.

The patient returned to the ED 3 days later with painful umbilical bleeding (Figure 3). While there, the patient extracted a 1-cm stone from the lesion, consistent with the calcification visualized on CT scan. Computed tomographic virtual cystoscopy showed no connection between the bladder and umbilicus. He was diagnosed with an umbilical-urachal sinus. Complete surgical excision was recommended and performed by urology without complication.

We report an unusual presentation of a symptomatic urachal remnant in an adult. During embryogenesis, the urachus connects the umbilicus to the developing bladder and normally involutes during development. Incomplete regression can cause rare pathological urachal anomalies. The clinical presentation is nonspecific and differs between children and adults, with most cases presenting during infancy or childhood.¹ Pediatric urachal abnormalities often present with umbilical drainage, abdominal pain, a palpable mass, an abnormal appearance of the umbilicus, or urinary tract infections.^2,3 In adults, the most common symptoms include hematuria, pain, or dysuria. Alternatively, they may be asympomatic³ or present with periumbilical dermatitis⁴ or abscess. Rodrigues and Gandhi⁵ reported another case of a symptomatic calculus formed within a urachal remnant. Calcifications in urachal remnants are rare and usually are reported as incidental radiologic findings.

Overall, visible umbilical masses occur infrequently. In addition to urachal anomalies, the differential diagnosis includes several benign and malignant pathologies. Benign causes include epidermoid cysts, foreign body granulomas, pyogenic granulomas, abscesses, hamartomas, nevi, hemangiomas, dermatofibromas, neurofibromas, lipomas, granular cell tumors, desmoid tumors, keloid scars, omphaliths, hernias, or omphalomesenteric duct remnants.⁶ Primary malignancies (eg, skin cancers, urachal adenocarcinoma, mesenchymal tumors) or metastasis (ie, Sister Mary Joseph nodule) also can present as umbilical nodules.

The wide range of clinical presentations of urachal anomalies combined with the rarity make diagnosis difficult. Thus, it is essential to have a high index of suspicion and awareness of how they can present. Ultrasonography and CT scan are useful tools in making the diagnosis. Urachal anomalies are prone to infection or can be associated with malignancy; therefore, timely and correct diagnosis is critical. Although surgical removal is the primary treatment for urachal anomalies, it may not be the primary treatment of the other entities included in the differential diagnosis of umbilical nodules. For example, the Sister Mary Joseph nodule can be associated with various primary malignancies, which should be treated accordingly.

To the Editor:

An otherwise healthy 26-year-old man presented to our outpatient clinic with a 15- to 20-mm, shiny, friable-appearing, red umbilical nodule with clear malodorous discharge (Figure 1). The lesion developed 2 weeks prior and gradually increased in size and discomfort. The patient reported mild associated abdominal pain. He had no fever, changes in urination or bowel movements, or prior history of umbilical growths or drainage. The abdomen was tender to palpation.

Differential diagnoses included pyogenic granuloma, umbilical hernia, epidermoid cyst or abscess, and malignancy (low suspicion). A biopsy was not performed due to concern for bleeding or communication with the bowel. A complete blood cell count, comprehensive metabolic panel, and urinalysis were unremarkable except for mild leukocytosis and elevated C-reactive protein. Ultrasonography revealed a 1.4×1.3-cm inflammatory umbilical mass with no communication with the bowel. The patient was referred to the emergency department (ED) for further evaluation. Computed tomography (CT) revealed periumbilical inflammation and an associated 1-cm calcification that appeared to be connected to a potential tract from the bladder, suggestive of a urachal remnant calcification (Figure 2). The patient was diagnosed with a persistent urachal remnant, discharged home with ciprofloxacin, and scheduled for a follow-up with urology.

The patient returned to the ED 3 days later with painful umbilical bleeding (Figure 3). While there, the patient extracted a 1-cm stone from the lesion, consistent with the calcification visualized on CT scan. Computed tomographic virtual cystoscopy showed no connection between the bladder and umbilicus. He was diagnosed with an umbilical-urachal sinus. Complete surgical excision was recommended and performed by urology without complication.

We report an unusual presentation of a symptomatic urachal remnant in an adult. During embryogenesis, the urachus connects the umbilicus to the developing bladder and normally involutes during development. Incomplete regression can cause rare pathological urachal anomalies. The clinical presentation is nonspecific and differs between children and adults, with most cases presenting during infancy or childhood.¹ Pediatric urachal abnormalities often present with umbilical drainage, abdominal pain, a palpable mass, an abnormal appearance of the umbilicus, or urinary tract infections.^2,3 In adults, the most common symptoms include hematuria, pain, or dysuria. Alternatively, they may be asympomatic³ or present with periumbilical dermatitis⁴ or abscess. Rodrigues and Gandhi⁵ reported another case of a symptomatic calculus formed within a urachal remnant. Calcifications in urachal remnants are rare and usually are reported as incidental radiologic findings.

Overall, visible umbilical masses occur infrequently. In addition to urachal anomalies, the differential diagnosis includes several benign and malignant pathologies. Benign causes include epidermoid cysts, foreign body granulomas, pyogenic granulomas, abscesses, hamartomas, nevi, hemangiomas, dermatofibromas, neurofibromas, lipomas, granular cell tumors, desmoid tumors, keloid scars, omphaliths, hernias, or omphalomesenteric duct remnants.⁶ Primary malignancies (eg, skin cancers, urachal adenocarcinoma, mesenchymal tumors) or metastasis (ie, Sister Mary Joseph nodule) also can present as umbilical nodules.

The wide range of clinical presentations of urachal anomalies combined with the rarity make diagnosis difficult. Thus, it is essential to have a high index of suspicion and awareness of how they can present. Ultrasonography and CT scan are useful tools in making the diagnosis. Urachal anomalies are prone to infection or can be associated with malignancy; therefore, timely and correct diagnosis is critical. Although surgical removal is the primary treatment for urachal anomalies, it may not be the primary treatment of the other entities included in the differential diagnosis of umbilical nodules. For example, the Sister Mary Joseph nodule can be associated with various primary malignancies, which should be treated accordingly.

To the Editor:

Postirradiation pseudosclerodermatous panniculitis (PIPP) is a rarely reported complication of megavoltage external beam radiotherapy that was first identified in 1993 by Winkelmann et al.¹ The condition presents as an erythematous or hyperpigmented indurated plaque at a site of prior radiotherapy. Lesions caused by PIPP most commonly arise several months after treatment, although they may emerge up to 17 years following exposure.² Herein, we report a rare case of a patient with PIPP occurring on the leg who previously had been treated for Kaposi sarcoma.

An 84-year-old woman presented with a tender plaque on the right lower leg of 2 months’ duration. Her medical history was remarkable for Kaposi sarcoma, with multiple sites on the body treated with megavoltage external beam radiotherapy during the prior 4 years. The most recent treatment occurred 8 months prior to presentation, at which time she had undergone radiotherapy for lesions on the posterior lower right leg. Physical examination demonstrated a hyperpigmented and indurated plaque at the treatment site (Figure 1). Skin biopsy results showed a mildly sclerotic dermis with atypical radiation fibroblasts scattered interstitially between collagen bundles, and a lobular panniculitis with degenerated adipocytes and foamy histiocytes (Figure 2). Hyalinized dermal vessels also were present. Based on the constellation of these biopsy findings, a diagnosis of PIPP was made.

The diagnosis of PIPP is challenging and invariably requires histologic examination. Clinically, the differential diagnosis includes cutaneous metastasis of the primary neoplasm, cellulitis, lipodermatosclerosis, morphea, and chronic radiation dermatitis.

Histologically, PIPP is characterized by a lobular panniculitis without vasculitis. Typical findings include the presence of centrilobular necrotic adipocytes along with a foamy histiocytic infiltrate containing lipophagic granulomas at the periphery of the fat lobules. Septal thickening and sclerosis around fat lobules also have been described, and dermal changes associated with chronic radiation dermatitis, such as papillary dermal sclerosis, endothelial swelling, vascular hyaline arteriosclerosis, and atypical star-shaped radiation fibroblasts, may be present.² Features of radiation-induced vasculopathy commonly are seen, although the appearance of these features varies over time. Intimal injury and mural thrombosis can develop within 5 years of radiation therapy, fibrosis of the vessel wall can occur within 10 years of radiation therapy, and atherosclerosis and periarterial fibrosis can appear within 20 years of radiation therapy.^2,3 The histologic findings in our patient showed characteristic dermal findings seen in radiation dermatitis in addition to a lobular panniculitis with foamy histiocytes and mild vessel damage.

In contrast, lipodermatosclerosis is a septal and lobular panniculitis with septal fibrosis. Membranocystic fat necrosis is present, characterized by fat microcysts lined by feathery eosinophilic material. Stasis changes in the dermis and epidermis are accompanied by a mild perivascular lymphocytic infiltrate.

Patients with traumatic panniculitis, which also may enter the clinical differential diagnosis of PIPP, often demonstrate nonspecific histologic changes. Early lesions show a perivascular infiltrate of lymphocytes and macrophages. Evolving lesions show variably sized fat microcysts surrounded by histiocytes, in addition to possible calcifications and a foreign-body giant cell reaction. A fibrous capsule may develop, surrounding the fat necrosis to form a mobile encapsulated lipoma. Late lesions frequently demonstrate lipomembranous changes and calcium deposits.⁴

To date, nearly all cases of PIPP in the literature have been described in breast cancer patients.^1,2,5,6 However, Sandoval et al⁷ reported a case of PIPP occurring in the leg of a patient after radiotherapy for a soft tissue sarcoma. Similar to our patient, this patient presented with a painful, dully erythematous, indurated plaque, although her symptoms arose 5 years after radiotherapy.

Megavoltage external beam radiotherapy has become a widely used modality in the treatment of various cancers. As such, PIPP may represent an underdiagnosed condition with potential cases remaining unidentified when the clinical differential diagnosis does not lead to biopsy. Effective therapies have yet to be widely reported, and our patient failed to experience notable improvement with either topical or intralesional corticosteroids. Further studies are needed in order to address this knowledge gap.

To the Editor:

Postirradiation pseudosclerodermatous panniculitis (PIPP) is a rarely reported complication of megavoltage external beam radiotherapy that was first identified in 1993 by Winkelmann et al.¹ The condition presents as an erythematous or hyperpigmented indurated plaque at a site of prior radiotherapy. Lesions caused by PIPP most commonly arise several months after treatment, although they may emerge up to 17 years following exposure.² Herein, we report a rare case of a patient with PIPP occurring on the leg who previously had been treated for Kaposi sarcoma.

An 84-year-old woman presented with a tender plaque on the right lower leg of 2 months’ duration. Her medical history was remarkable for Kaposi sarcoma, with multiple sites on the body treated with megavoltage external beam radiotherapy during the prior 4 years. The most recent treatment occurred 8 months prior to presentation, at which time she had undergone radiotherapy for lesions on the posterior lower right leg. Physical examination demonstrated a hyperpigmented and indurated plaque at the treatment site (Figure 1). Skin biopsy results showed a mildly sclerotic dermis with atypical radiation fibroblasts scattered interstitially between collagen bundles, and a lobular panniculitis with degenerated adipocytes and foamy histiocytes (Figure 2). Hyalinized dermal vessels also were present. Based on the constellation of these biopsy findings, a diagnosis of PIPP was made.

The diagnosis of PIPP is challenging and invariably requires histologic examination. Clinically, the differential diagnosis includes cutaneous metastasis of the primary neoplasm, cellulitis, lipodermatosclerosis, morphea, and chronic radiation dermatitis.

Histologically, PIPP is characterized by a lobular panniculitis without vasculitis. Typical findings include the presence of centrilobular necrotic adipocytes along with a foamy histiocytic infiltrate containing lipophagic granulomas at the periphery of the fat lobules. Septal thickening and sclerosis around fat lobules also have been described, and dermal changes associated with chronic radiation dermatitis, such as papillary dermal sclerosis, endothelial swelling, vascular hyaline arteriosclerosis, and atypical star-shaped radiation fibroblasts, may be present.² Features of radiation-induced vasculopathy commonly are seen, although the appearance of these features varies over time. Intimal injury and mural thrombosis can develop within 5 years of radiation therapy, fibrosis of the vessel wall can occur within 10 years of radiation therapy, and atherosclerosis and periarterial fibrosis can appear within 20 years of radiation therapy.^2,3 The histologic findings in our patient showed characteristic dermal findings seen in radiation dermatitis in addition to a lobular panniculitis with foamy histiocytes and mild vessel damage.

In contrast, lipodermatosclerosis is a septal and lobular panniculitis with septal fibrosis. Membranocystic fat necrosis is present, characterized by fat microcysts lined by feathery eosinophilic material. Stasis changes in the dermis and epidermis are accompanied by a mild perivascular lymphocytic infiltrate.

Patients with traumatic panniculitis, which also may enter the clinical differential diagnosis of PIPP, often demonstrate nonspecific histologic changes. Early lesions show a perivascular infiltrate of lymphocytes and macrophages. Evolving lesions show variably sized fat microcysts surrounded by histiocytes, in addition to possible calcifications and a foreign-body giant cell reaction. A fibrous capsule may develop, surrounding the fat necrosis to form a mobile encapsulated lipoma. Late lesions frequently demonstrate lipomembranous changes and calcium deposits.⁴

To date, nearly all cases of PIPP in the literature have been described in breast cancer patients.^1,2,5,6 However, Sandoval et al⁷ reported a case of PIPP occurring in the leg of a patient after radiotherapy for a soft tissue sarcoma. Similar to our patient, this patient presented with a painful, dully erythematous, indurated plaque, although her symptoms arose 5 years after radiotherapy.

Megavoltage external beam radiotherapy has become a widely used modality in the treatment of various cancers. As such, PIPP may represent an underdiagnosed condition with potential cases remaining unidentified when the clinical differential diagnosis does not lead to biopsy. Effective therapies have yet to be widely reported, and our patient failed to experience notable improvement with either topical or intralesional corticosteroids. Further studies are needed in order to address this knowledge gap.

To the Editor:

Postirradiation pseudosclerodermatous panniculitis (PIPP) is a rarely reported complication of megavoltage external beam radiotherapy that was first identified in 1993 by Winkelmann et al.¹ The condition presents as an erythematous or hyperpigmented indurated plaque at a site of prior radiotherapy. Lesions caused by PIPP most commonly arise several months after treatment, although they may emerge up to 17 years following exposure.² Herein, we report a rare case of a patient with PIPP occurring on the leg who previously had been treated for Kaposi sarcoma.

An 84-year-old woman presented with a tender plaque on the right lower leg of 2 months’ duration. Her medical history was remarkable for Kaposi sarcoma, with multiple sites on the body treated with megavoltage external beam radiotherapy during the prior 4 years. The most recent treatment occurred 8 months prior to presentation, at which time she had undergone radiotherapy for lesions on the posterior lower right leg. Physical examination demonstrated a hyperpigmented and indurated plaque at the treatment site (Figure 1). Skin biopsy results showed a mildly sclerotic dermis with atypical radiation fibroblasts scattered interstitially between collagen bundles, and a lobular panniculitis with degenerated adipocytes and foamy histiocytes (Figure 2). Hyalinized dermal vessels also were present. Based on the constellation of these biopsy findings, a diagnosis of PIPP was made.

The diagnosis of PIPP is challenging and invariably requires histologic examination. Clinically, the differential diagnosis includes cutaneous metastasis of the primary neoplasm, cellulitis, lipodermatosclerosis, morphea, and chronic radiation dermatitis.

Histologically, PIPP is characterized by a lobular panniculitis without vasculitis. Typical findings include the presence of centrilobular necrotic adipocytes along with a foamy histiocytic infiltrate containing lipophagic granulomas at the periphery of the fat lobules. Septal thickening and sclerosis around fat lobules also have been described, and dermal changes associated with chronic radiation dermatitis, such as papillary dermal sclerosis, endothelial swelling, vascular hyaline arteriosclerosis, and atypical star-shaped radiation fibroblasts, may be present.² Features of radiation-induced vasculopathy commonly are seen, although the appearance of these features varies over time. Intimal injury and mural thrombosis can develop within 5 years of radiation therapy, fibrosis of the vessel wall can occur within 10 years of radiation therapy, and atherosclerosis and periarterial fibrosis can appear within 20 years of radiation therapy.^2,3 The histologic findings in our patient showed characteristic dermal findings seen in radiation dermatitis in addition to a lobular panniculitis with foamy histiocytes and mild vessel damage.

In contrast, lipodermatosclerosis is a septal and lobular panniculitis with septal fibrosis. Membranocystic fat necrosis is present, characterized by fat microcysts lined by feathery eosinophilic material. Stasis changes in the dermis and epidermis are accompanied by a mild perivascular lymphocytic infiltrate.

Patients with traumatic panniculitis, which also may enter the clinical differential diagnosis of PIPP, often demonstrate nonspecific histologic changes. Early lesions show a perivascular infiltrate of lymphocytes and macrophages. Evolving lesions show variably sized fat microcysts surrounded by histiocytes, in addition to possible calcifications and a foreign-body giant cell reaction. A fibrous capsule may develop, surrounding the fat necrosis to form a mobile encapsulated lipoma. Late lesions frequently demonstrate lipomembranous changes and calcium deposits.⁴

To date, nearly all cases of PIPP in the literature have been described in breast cancer patients.^1,2,5,6 However, Sandoval et al⁷ reported a case of PIPP occurring in the leg of a patient after radiotherapy for a soft tissue sarcoma. Similar to our patient, this patient presented with a painful, dully erythematous, indurated plaque, although her symptoms arose 5 years after radiotherapy.

Megavoltage external beam radiotherapy has become a widely used modality in the treatment of various cancers. As such, PIPP may represent an underdiagnosed condition with potential cases remaining unidentified when the clinical differential diagnosis does not lead to biopsy. Effective therapies have yet to be widely reported, and our patient failed to experience notable improvement with either topical or intralesional corticosteroids. Further studies are needed in order to address this knowledge gap.

The Diagnosis: Tufted Angioma

Histopathology revealed discrete lobules of closely packed capillaries with bland endothelial cells throughout the upper and lower dermis (Figure 1). The surrounding crescentlike vessels and lymphatics stained with D2-40 (Figure 2). These histologic findings were consistent with tufted angioma, and the patient elected for observation.

Tufted angiomas are benign vascular lesions named for the tufted appearance of capillaries on histology.¹ They commonly present in children, with a lower incidence in adults and rare cases in pregnancy.² Tufted angiomas typically present as solitary, slowly expanding, erythematous macules, plaques, or nodules on the neck or trunk ranging in size from less than 1 to 10 cm.^2-4 They can be histologically distinguished from other vascular tumors, including aggressive malignant neoplasms.¹

Tufted angiomas are identified by characteristic “cannon ball tufts” of capillaries in the dermis and subcutis at low power.^3,5 Distinct cellular lobules may be found bulging into thin-walled vascular channels at the margins of the lobules in the dermis and subcutis (Figure 3).⁴ The lobules are formed by cells with spindle-shaped nuclei.⁶ Some mitotic figures may be present, but no cellular atypia is seen.² The capillaries at the periphery appear as dilated semilunar vessels.⁴ Dilated lymphatics, which stain with D2-40, can be found at the periphery of the tufted capillaries and throughout the remaining dermis.^3,4

Tufted angiomas may arise independently in adults but also have been associated with conditions such as pregnancy. Omori et al⁷ identified an acquired tufted angioma in pregnancy that was positive for estrogen and progesterone receptors. Reports of tufted angiomas in pregnancy vary; some are multiple lesions, some regress postpartum, and some undergo successful surgical treatment.^3,5

Vascular lesions such as tufted angiomas specifically may appear in pregnancy due to a high-volume state with vasodilation and increased vascular proliferation. Although tumor angiogenesis has been linked to specific growth factors and cytokines, it has been hypothesized that the systemic hormones of pregnancy such as human chorionic gonadotropin, estradiol, and progesterone also shift the body to a more angiogenic state.⁸ In a study of cutaneous changes in pregnant women (N=905), 41% developed a vascular skin change, including spider veins, varicosities, hemangiomas, and granulomas.⁹ The most common vascular tumor in pregnancy is pyogenic granuloma. Pyogenic granulomas are small, solitary, friable papules that commonly are found on the hands, forearms, face, or in the mouth; histologically they demonstrate dilated capillaries in lobular structures accompanied by larger thick-walled vessels.^3,10,11

Tufted angiomas may mimic a variety of other conditions. Epithelioid hemangioma, considered by some to be on the same morphologic spectrum as angiolymphoid hyperplasia with eosinophilia, classically occurs in young adults on the head and in the neck region. It histologically demonstrates a lobular appearance at low power; however, these lobules are made up of vessels with histiocytoid to epithelioid endothelial cells surrounded by a prominent inflammatory infiltrate consisting of lymphocytes and eosinophils.¹²

Kaposi sarcoma may appear on the neck but most often presents as macules and patches on the extremities that may form nodules with a rubbery consistency. In tufted angiomas, the cellular nodules with dilated channels at the margins bear a resemblance to Kaposi sarcoma or kaposiform hemangioendothelioma; however, in tufted angiomas the lobules are composed of bland spindle cells and slitlike vessels at the periphery.^3,13,14 Tufted angiomas are negative for human herpesvirus 8 and typically do not have an associated inflammatory infiltrate with plasma cells.^11,15

Moreover, it is important to differentiate tufted angioma from a cutaneous manifestation of an underlying malignancy, which has been described previously in cases of breast cancer.^16,17 Our case illustrates a rare vascular tumor arising in the novel context of a pregnant patient with breast cancer. Distinguishing tufted angioma from other benign or malignant vascular tumors is necessary to avoid inappropriate therapeutic interventions.

The Diagnosis: Tufted Angioma

Histopathology revealed discrete lobules of closely packed capillaries with bland endothelial cells throughout the upper and lower dermis (Figure 1). The surrounding crescentlike vessels and lymphatics stained with D2-40 (Figure 2). These histologic findings were consistent with tufted angioma, and the patient elected for observation.

Tufted angiomas are benign vascular lesions named for the tufted appearance of capillaries on histology.¹ They commonly present in children, with a lower incidence in adults and rare cases in pregnancy.² Tufted angiomas typically present as solitary, slowly expanding, erythematous macules, plaques, or nodules on the neck or trunk ranging in size from less than 1 to 10 cm.^2-4 They can be histologically distinguished from other vascular tumors, including aggressive malignant neoplasms.¹

Tufted angiomas are identified by characteristic “cannon ball tufts” of capillaries in the dermis and subcutis at low power.^3,5 Distinct cellular lobules may be found bulging into thin-walled vascular channels at the margins of the lobules in the dermis and subcutis (Figure 3).⁴ The lobules are formed by cells with spindle-shaped nuclei.⁶ Some mitotic figures may be present, but no cellular atypia is seen.² The capillaries at the periphery appear as dilated semilunar vessels.⁴ Dilated lymphatics, which stain with D2-40, can be found at the periphery of the tufted capillaries and throughout the remaining dermis.^3,4

Tufted angiomas may arise independently in adults but also have been associated with conditions such as pregnancy. Omori et al⁷ identified an acquired tufted angioma in pregnancy that was positive for estrogen and progesterone receptors. Reports of tufted angiomas in pregnancy vary; some are multiple lesions, some regress postpartum, and some undergo successful surgical treatment.^3,5

Vascular lesions such as tufted angiomas specifically may appear in pregnancy due to a high-volume state with vasodilation and increased vascular proliferation. Although tumor angiogenesis has been linked to specific growth factors and cytokines, it has been hypothesized that the systemic hormones of pregnancy such as human chorionic gonadotropin, estradiol, and progesterone also shift the body to a more angiogenic state.⁸ In a study of cutaneous changes in pregnant women (N=905), 41% developed a vascular skin change, including spider veins, varicosities, hemangiomas, and granulomas.⁹ The most common vascular tumor in pregnancy is pyogenic granuloma. Pyogenic granulomas are small, solitary, friable papules that commonly are found on the hands, forearms, face, or in the mouth; histologically they demonstrate dilated capillaries in lobular structures accompanied by larger thick-walled vessels.^3,10,11

Tufted angiomas may mimic a variety of other conditions. Epithelioid hemangioma, considered by some to be on the same morphologic spectrum as angiolymphoid hyperplasia with eosinophilia, classically occurs in young adults on the head and in the neck region. It histologically demonstrates a lobular appearance at low power; however, these lobules are made up of vessels with histiocytoid to epithelioid endothelial cells surrounded by a prominent inflammatory infiltrate consisting of lymphocytes and eosinophils.¹²

Kaposi sarcoma may appear on the neck but most often presents as macules and patches on the extremities that may form nodules with a rubbery consistency. In tufted angiomas, the cellular nodules with dilated channels at the margins bear a resemblance to Kaposi sarcoma or kaposiform hemangioendothelioma; however, in tufted angiomas the lobules are composed of bland spindle cells and slitlike vessels at the periphery.^3,13,14 Tufted angiomas are negative for human herpesvirus 8 and typically do not have an associated inflammatory infiltrate with plasma cells.^11,15

Moreover, it is important to differentiate tufted angioma from a cutaneous manifestation of an underlying malignancy, which has been described previously in cases of breast cancer.^16,17 Our case illustrates a rare vascular tumor arising in the novel context of a pregnant patient with breast cancer. Distinguishing tufted angioma from other benign or malignant vascular tumors is necessary to avoid inappropriate therapeutic interventions.

The Diagnosis: Tufted Angioma

Histopathology revealed discrete lobules of closely packed capillaries with bland endothelial cells throughout the upper and lower dermis (Figure 1). The surrounding crescentlike vessels and lymphatics stained with D2-40 (Figure 2). These histologic findings were consistent with tufted angioma, and the patient elected for observation.

Tufted angiomas are benign vascular lesions named for the tufted appearance of capillaries on histology.¹ They commonly present in children, with a lower incidence in adults and rare cases in pregnancy.² Tufted angiomas typically present as solitary, slowly expanding, erythematous macules, plaques, or nodules on the neck or trunk ranging in size from less than 1 to 10 cm.^2-4 They can be histologically distinguished from other vascular tumors, including aggressive malignant neoplasms.¹

Tufted angiomas are identified by characteristic “cannon ball tufts” of capillaries in the dermis and subcutis at low power.^3,5 Distinct cellular lobules may be found bulging into thin-walled vascular channels at the margins of the lobules in the dermis and subcutis (Figure 3).⁴ The lobules are formed by cells with spindle-shaped nuclei.⁶ Some mitotic figures may be present, but no cellular atypia is seen.² The capillaries at the periphery appear as dilated semilunar vessels.⁴ Dilated lymphatics, which stain with D2-40, can be found at the periphery of the tufted capillaries and throughout the remaining dermis.^3,4

Tufted angiomas may arise independently in adults but also have been associated with conditions such as pregnancy. Omori et al⁷ identified an acquired tufted angioma in pregnancy that was positive for estrogen and progesterone receptors. Reports of tufted angiomas in pregnancy vary; some are multiple lesions, some regress postpartum, and some undergo successful surgical treatment.^3,5

Vascular lesions such as tufted angiomas specifically may appear in pregnancy due to a high-volume state with vasodilation and increased vascular proliferation. Although tumor angiogenesis has been linked to specific growth factors and cytokines, it has been hypothesized that the systemic hormones of pregnancy such as human chorionic gonadotropin, estradiol, and progesterone also shift the body to a more angiogenic state.⁸ In a study of cutaneous changes in pregnant women (N=905), 41% developed a vascular skin change, including spider veins, varicosities, hemangiomas, and granulomas.⁹ The most common vascular tumor in pregnancy is pyogenic granuloma. Pyogenic granulomas are small, solitary, friable papules that commonly are found on the hands, forearms, face, or in the mouth; histologically they demonstrate dilated capillaries in lobular structures accompanied by larger thick-walled vessels.^3,10,11

Tufted angiomas may mimic a variety of other conditions. Epithelioid hemangioma, considered by some to be on the same morphologic spectrum as angiolymphoid hyperplasia with eosinophilia, classically occurs in young adults on the head and in the neck region. It histologically demonstrates a lobular appearance at low power; however, these lobules are made up of vessels with histiocytoid to epithelioid endothelial cells surrounded by a prominent inflammatory infiltrate consisting of lymphocytes and eosinophils.¹²

Kaposi sarcoma may appear on the neck but most often presents as macules and patches on the extremities that may form nodules with a rubbery consistency. In tufted angiomas, the cellular nodules with dilated channels at the margins bear a resemblance to Kaposi sarcoma or kaposiform hemangioendothelioma; however, in tufted angiomas the lobules are composed of bland spindle cells and slitlike vessels at the periphery.^3,13,14 Tufted angiomas are negative for human herpesvirus 8 and typically do not have an associated inflammatory infiltrate with plasma cells.^11,15

Moreover, it is important to differentiate tufted angioma from a cutaneous manifestation of an underlying malignancy, which has been described previously in cases of breast cancer.^16,17 Our case illustrates a rare vascular tumor arising in the novel context of a pregnant patient with breast cancer. Distinguishing tufted angioma from other benign or malignant vascular tumors is necessary to avoid inappropriate therapeutic interventions.

Case Report

A 60-year-old man presented with eroded areas in the mouth and blistering eruptions on the scalp, face, trunk, arms, and legs. He initially presented to an outside hospital 4 years prior and was treated with oral prednisone 50 mg daily, to which the eruptions responded rapidly; however, following a nearly 5-mg reduction of the dose per week by the patient and irregular oral administration, he experienced several episodes of recurrence, but he could not remember the exact dosage of prednisone he had taken during that period. Subsequently, he was admitted to our hospital because of large areas of erythema and erosions on the scalp, trunk, arms, and legs.

Since starting the prednisone regimen 4 years prior, the patient had experienced onset of hypertension, diabetes, glaucoma, cataracts, optic nerve atrophy, aseptic necrosis of the femoral head, and osteoporosis. Biopsy of a new skin lesion revealed suprabasal acantholysis (Figure 1). Direct immunofluorescence showed epidermal intercellular deposition of IgG and complement component 3. Laboratory testing showed a desmoglein 1 level of 142 U/mL (reference range, <14 U/mL) and desmoglein 3 level of 150 U/mL (reference range, <14 U/mL). Liver and kidney function; routine blood and urine tests; and antinuclear antibody, hepatitis B and C antibodies, syphilis, and human immunodeficiency virus antibody levels were normal. The biopsy and immunofluorescence results combined with clinical feature were consistent with a diagnosis of pemphigus vulgaris (PV).

The patient initially was started again prednisone 50 mg daily, to which the skin eruptions responded, and 2 weeks later, the disease was considered controlled. The prednisone dosage was tapered to 20 mg daily 3 months later with no new blister formation. However, 2 weeks later, the patient was diagnosed by a tuberculosis specialist with pulmonary tuberculosis, and a daily regimen of isoniazid, rifampicin, ethambutol, and levofloxacin was instituted.

Ten days after starting antituberculosis therapy, the patient developed new erythematous blisters that could not be controlled and self-adjusted the prednisone dose to 50 mg daily. Two months later, blister formation continued.

Six months after the initial presentation, the patient returned to our hospital because of uncontrollable rashes (Figure 2). On admission, he had a Pemphigus Disease Area Index (PDAI) score of 32 with disease involving 30% of the body surface area. Laboratory testing showed a desmoglein 1 level of 233 U/mL and desmoglein 3 level of 228 U/mL. A tuberculosis specialist from an outside hospital was consulted to evaluate the patient’s condition and assist in treatment. Based on findings from a pulmonary computed tomography scan, which showed the inflammation was considerably absorbed, treatment was adjusted to stop using ethambutol and levofloxacin and continue rifampicin and isoniazid. For the PV, prednisone was titrated upward to 75 mg daily, mycophenolate mofetil (MMF) 1 g twice daily was added, and IVIG 400 mg/kg daily was administered for 7 days. After 3 weeks, the rash still expanded.

In considering possible interactions between the drugs, we consulted the literature and found reports^1-3 that rifampicin accelerated glucocorticoid metabolism, of which the tuberculosis specialist that we consulted was not aware. Therefore, rifampicin was stopped, and the antituberculosis therapy was adjusted to levofloxacin and isoniazid. Meanwhile, the steroid was changed to methylprednisolone 120 mg daily for 3 days, then to 80 mg daily for 2 days.

After 5 days, the rash was controlled with no new development and the patient was discharged. He continued on prednisone 80 mg daily and MMF 1 g twice daily.

At 2-month follow-up, no new rash had developed. The patient had already self-discontinued the MMF for 1 month because it was difficult to obtain at local hospitals. The prednisone was reduced to 40 mg daily. Pulmonary computed tomography showed no signs of reactivation of tuberculosis.

Comment

The tuberculostatic compound rifampin induces expression of a number of drug metabolism-related genes associated with cytochromes (especially cytochrome P450 3A4), multidrug resistance (P-glycoprotein and multidrug resistance proteins 1 and 2), uridine 5’-diphospho-glucuronosyltransferase, monoamine oxidases, and glutathione S-transferases.

Drugs that depend on these enzymes for their metabolism are prone to drug interactions when co-administered with rifampicin.^4,5 It has been reported that rifampicin reduces the area under the concentration–time curve (AUC) of prednisolone by approximately 30% to 60%; some authors have suggested that, if rifampicin has to be prescribed, a 2- to 3-fold increase in the prednisolone dosage might be indicated.^1,4,6,7 Rifampicin also can influence immunosuppressive drugs in organ transplant recipients; for example, an 11-day course of rifampicin 600 mg daily was found to reduce the AUC of oral cyclosporine by approximately 70% and of intravenous cyclosporine by 28%.^4,8 Similarly, treatment with rifampicin 600 mg daily for 18 days reduced the AUC of oral tacrolimus by 68% and of intravenous tacrolimus by 35%.^4,9

Rifampicin causes a marked reduction in dose-corrected mycophenolic acid exposure when administered simultaneously with MMF through induction of glucuronidation activity and inhibition of enterohepatic recirculation.^5,10In in vitro studies, rifampin and other cytochrome P450 inducers have been identified as potentially useful for increasing the rate of cyclophosphamide and ifosfamide (an isomeric analogue of cyclophosphamide) 4-hydroxylation in the human liver in a manner that could have a favorable impact on the clinical pharmacokinetics of these anticancer prodrugs.¹¹ However, clinical analysis of 16 patients indicated that co-administration of ifosfamide with rifampin did not result in changes in the pharmacokinetics of the parent drug or its metabolites.¹²

The steroids and immunosuppressants mentioned above are widely used in the treatment of autoimmune diseases and drug hypersensitivity in dermatology. Drug interactions should be considered and drug concentrations closely monitored in cases of rifampin co-administration.

Conclusion

In our patient, the use of rifapentine resulted in a recurrence of previously controlled PV and resistance to treatment. The patient’s disease was quickly controlled after discontinuation of rifampicin and with a short-term course of high-dose methylprednisolone and remained stable when the dosages of MMF and prednisone were reduced. This case serves as a reminder for clinicians to consider a drug interaction when treatment fails in order to avoid harming patients, especially those who have an autoimmune disease.

Case Report

A 60-year-old man presented with eroded areas in the mouth and blistering eruptions on the scalp, face, trunk, arms, and legs. He initially presented to an outside hospital 4 years prior and was treated with oral prednisone 50 mg daily, to which the eruptions responded rapidly; however, following a nearly 5-mg reduction of the dose per week by the patient and irregular oral administration, he experienced several episodes of recurrence, but he could not remember the exact dosage of prednisone he had taken during that period. Subsequently, he was admitted to our hospital because of large areas of erythema and erosions on the scalp, trunk, arms, and legs.

Since starting the prednisone regimen 4 years prior, the patient had experienced onset of hypertension, diabetes, glaucoma, cataracts, optic nerve atrophy, aseptic necrosis of the femoral head, and osteoporosis. Biopsy of a new skin lesion revealed suprabasal acantholysis (Figure 1). Direct immunofluorescence showed epidermal intercellular deposition of IgG and complement component 3. Laboratory testing showed a desmoglein 1 level of 142 U/mL (reference range, <14 U/mL) and desmoglein 3 level of 150 U/mL (reference range, <14 U/mL). Liver and kidney function; routine blood and urine tests; and antinuclear antibody, hepatitis B and C antibodies, syphilis, and human immunodeficiency virus antibody levels were normal. The biopsy and immunofluorescence results combined with clinical feature were consistent with a diagnosis of pemphigus vulgaris (PV).

The patient initially was started again prednisone 50 mg daily, to which the skin eruptions responded, and 2 weeks later, the disease was considered controlled. The prednisone dosage was tapered to 20 mg daily 3 months later with no new blister formation. However, 2 weeks later, the patient was diagnosed by a tuberculosis specialist with pulmonary tuberculosis, and a daily regimen of isoniazid, rifampicin, ethambutol, and levofloxacin was instituted.

Ten days after starting antituberculosis therapy, the patient developed new erythematous blisters that could not be controlled and self-adjusted the prednisone dose to 50 mg daily. Two months later, blister formation continued.

Six months after the initial presentation, the patient returned to our hospital because of uncontrollable rashes (Figure 2). On admission, he had a Pemphigus Disease Area Index (PDAI) score of 32 with disease involving 30% of the body surface area. Laboratory testing showed a desmoglein 1 level of 233 U/mL and desmoglein 3 level of 228 U/mL. A tuberculosis specialist from an outside hospital was consulted to evaluate the patient’s condition and assist in treatment. Based on findings from a pulmonary computed tomography scan, which showed the inflammation was considerably absorbed, treatment was adjusted to stop using ethambutol and levofloxacin and continue rifampicin and isoniazid. For the PV, prednisone was titrated upward to 75 mg daily, mycophenolate mofetil (MMF) 1 g twice daily was added, and IVIG 400 mg/kg daily was administered for 7 days. After 3 weeks, the rash still expanded.

In considering possible interactions between the drugs, we consulted the literature and found reports^1-3 that rifampicin accelerated glucocorticoid metabolism, of which the tuberculosis specialist that we consulted was not aware. Therefore, rifampicin was stopped, and the antituberculosis therapy was adjusted to levofloxacin and isoniazid. Meanwhile, the steroid was changed to methylprednisolone 120 mg daily for 3 days, then to 80 mg daily for 2 days.

After 5 days, the rash was controlled with no new development and the patient was discharged. He continued on prednisone 80 mg daily and MMF 1 g twice daily.

At 2-month follow-up, no new rash had developed. The patient had already self-discontinued the MMF for 1 month because it was difficult to obtain at local hospitals. The prednisone was reduced to 40 mg daily. Pulmonary computed tomography showed no signs of reactivation of tuberculosis.

Comment

The tuberculostatic compound rifampin induces expression of a number of drug metabolism-related genes associated with cytochromes (especially cytochrome P450 3A4), multidrug resistance (P-glycoprotein and multidrug resistance proteins 1 and 2), uridine 5’-diphospho-glucuronosyltransferase, monoamine oxidases, and glutathione S-transferases.

Drugs that depend on these enzymes for their metabolism are prone to drug interactions when co-administered with rifampicin.^4,5 It has been reported that rifampicin reduces the area under the concentration–time curve (AUC) of prednisolone by approximately 30% to 60%; some authors have suggested that, if rifampicin has to be prescribed, a 2- to 3-fold increase in the prednisolone dosage might be indicated.^1,4,6,7 Rifampicin also can influence immunosuppressive drugs in organ transplant recipients; for example, an 11-day course of rifampicin 600 mg daily was found to reduce the AUC of oral cyclosporine by approximately 70% and of intravenous cyclosporine by 28%.^4,8 Similarly, treatment with rifampicin 600 mg daily for 18 days reduced the AUC of oral tacrolimus by 68% and of intravenous tacrolimus by 35%.^4,9

Rifampicin causes a marked reduction in dose-corrected mycophenolic acid exposure when administered simultaneously with MMF through induction of glucuronidation activity and inhibition of enterohepatic recirculation.^5,10In in vitro studies, rifampin and other cytochrome P450 inducers have been identified as potentially useful for increasing the rate of cyclophosphamide and ifosfamide (an isomeric analogue of cyclophosphamide) 4-hydroxylation in the human liver in a manner that could have a favorable impact on the clinical pharmacokinetics of these anticancer prodrugs.¹¹ However, clinical analysis of 16 patients indicated that co-administration of ifosfamide with rifampin did not result in changes in the pharmacokinetics of the parent drug or its metabolites.¹²

The steroids and immunosuppressants mentioned above are widely used in the treatment of autoimmune diseases and drug hypersensitivity in dermatology. Drug interactions should be considered and drug concentrations closely monitored in cases of rifampin co-administration.

Conclusion

In our patient, the use of rifapentine resulted in a recurrence of previously controlled PV and resistance to treatment. The patient’s disease was quickly controlled after discontinuation of rifampicin and with a short-term course of high-dose methylprednisolone and remained stable when the dosages of MMF and prednisone were reduced. This case serves as a reminder for clinicians to consider a drug interaction when treatment fails in order to avoid harming patients, especially those who have an autoimmune disease.

Case Report

A 60-year-old man presented with eroded areas in the mouth and blistering eruptions on the scalp, face, trunk, arms, and legs. He initially presented to an outside hospital 4 years prior and was treated with oral prednisone 50 mg daily, to which the eruptions responded rapidly; however, following a nearly 5-mg reduction of the dose per week by the patient and irregular oral administration, he experienced several episodes of recurrence, but he could not remember the exact dosage of prednisone he had taken during that period. Subsequently, he was admitted to our hospital because of large areas of erythema and erosions on the scalp, trunk, arms, and legs.

Since starting the prednisone regimen 4 years prior, the patient had experienced onset of hypertension, diabetes, glaucoma, cataracts, optic nerve atrophy, aseptic necrosis of the femoral head, and osteoporosis. Biopsy of a new skin lesion revealed suprabasal acantholysis (Figure 1). Direct immunofluorescence showed epidermal intercellular deposition of IgG and complement component 3. Laboratory testing showed a desmoglein 1 level of 142 U/mL (reference range, <14 U/mL) and desmoglein 3 level of 150 U/mL (reference range, <14 U/mL). Liver and kidney function; routine blood and urine tests; and antinuclear antibody, hepatitis B and C antibodies, syphilis, and human immunodeficiency virus antibody levels were normal. The biopsy and immunofluorescence results combined with clinical feature were consistent with a diagnosis of pemphigus vulgaris (PV).

The patient initially was started again prednisone 50 mg daily, to which the skin eruptions responded, and 2 weeks later, the disease was considered controlled. The prednisone dosage was tapered to 20 mg daily 3 months later with no new blister formation. However, 2 weeks later, the patient was diagnosed by a tuberculosis specialist with pulmonary tuberculosis, and a daily regimen of isoniazid, rifampicin, ethambutol, and levofloxacin was instituted.

Ten days after starting antituberculosis therapy, the patient developed new erythematous blisters that could not be controlled and self-adjusted the prednisone dose to 50 mg daily. Two months later, blister formation continued.

Six months after the initial presentation, the patient returned to our hospital because of uncontrollable rashes (Figure 2). On admission, he had a Pemphigus Disease Area Index (PDAI) score of 32 with disease involving 30% of the body surface area. Laboratory testing showed a desmoglein 1 level of 233 U/mL and desmoglein 3 level of 228 U/mL. A tuberculosis specialist from an outside hospital was consulted to evaluate the patient’s condition and assist in treatment. Based on findings from a pulmonary computed tomography scan, which showed the inflammation was considerably absorbed, treatment was adjusted to stop using ethambutol and levofloxacin and continue rifampicin and isoniazid. For the PV, prednisone was titrated upward to 75 mg daily, mycophenolate mofetil (MMF) 1 g twice daily was added, and IVIG 400 mg/kg daily was administered for 7 days. After 3 weeks, the rash still expanded.

In considering possible interactions between the drugs, we consulted the literature and found reports^1-3 that rifampicin accelerated glucocorticoid metabolism, of which the tuberculosis specialist that we consulted was not aware. Therefore, rifampicin was stopped, and the antituberculosis therapy was adjusted to levofloxacin and isoniazid. Meanwhile, the steroid was changed to methylprednisolone 120 mg daily for 3 days, then to 80 mg daily for 2 days.

After 5 days, the rash was controlled with no new development and the patient was discharged. He continued on prednisone 80 mg daily and MMF 1 g twice daily.

At 2-month follow-up, no new rash had developed. The patient had already self-discontinued the MMF for 1 month because it was difficult to obtain at local hospitals. The prednisone was reduced to 40 mg daily. Pulmonary computed tomography showed no signs of reactivation of tuberculosis.

Comment

The tuberculostatic compound rifampin induces expression of a number of drug metabolism-related genes associated with cytochromes (especially cytochrome P450 3A4), multidrug resistance (P-glycoprotein and multidrug resistance proteins 1 and 2), uridine 5’-diphospho-glucuronosyltransferase, monoamine oxidases, and glutathione S-transferases.

Drugs that depend on these enzymes for their metabolism are prone to drug interactions when co-administered with rifampicin.^4,5 It has been reported that rifampicin reduces the area under the concentration–time curve (AUC) of prednisolone by approximately 30% to 60%; some authors have suggested that, if rifampicin has to be prescribed, a 2- to 3-fold increase in the prednisolone dosage might be indicated.^1,4,6,7 Rifampicin also can influence immunosuppressive drugs in organ transplant recipients; for example, an 11-day course of rifampicin 600 mg daily was found to reduce the AUC of oral cyclosporine by approximately 70% and of intravenous cyclosporine by 28%.^4,8 Similarly, treatment with rifampicin 600 mg daily for 18 days reduced the AUC of oral tacrolimus by 68% and of intravenous tacrolimus by 35%.^4,9

Rifampicin causes a marked reduction in dose-corrected mycophenolic acid exposure when administered simultaneously with MMF through induction of glucuronidation activity and inhibition of enterohepatic recirculation.^5,10In in vitro studies, rifampin and other cytochrome P450 inducers have been identified as potentially useful for increasing the rate of cyclophosphamide and ifosfamide (an isomeric analogue of cyclophosphamide) 4-hydroxylation in the human liver in a manner that could have a favorable impact on the clinical pharmacokinetics of these anticancer prodrugs.¹¹ However, clinical analysis of 16 patients indicated that co-administration of ifosfamide with rifampin did not result in changes in the pharmacokinetics of the parent drug or its metabolites.¹²

The steroids and immunosuppressants mentioned above are widely used in the treatment of autoimmune diseases and drug hypersensitivity in dermatology. Drug interactions should be considered and drug concentrations closely monitored in cases of rifampin co-administration.

Conclusion

In our patient, the use of rifapentine resulted in a recurrence of previously controlled PV and resistance to treatment. The patient’s disease was quickly controlled after discontinuation of rifampicin and with a short-term course of high-dose methylprednisolone and remained stable when the dosages of MMF and prednisone were reduced. This case serves as a reminder for clinicians to consider a drug interaction when treatment fails in order to avoid harming patients, especially those who have an autoimmune disease.

To the Editor:

Several techniques can be used to destroy milia including electrocautery, electrodesiccation, and laser therapy. Manual extraction of milia uses a scalpel blade, needle, or stylet followed by the application of pressure to the lesion with a curette, comedone extractor, paper clip, cotton-tipped applicator, tongue blade, or hypodermic needle.^1-4 Many of these techniques fail to stabilize milia, particularly in sensitive areas such as around the eyes or mouth, which can make extraction challenging, inefficient, and painful for the patient. We report a novel technique that quickly and effectively removes milia with equipment commonly used in the practice of clinical dermatology.

A 74-year-old woman presented with an asymptomatic papule on the right lower vermilion border of several years' duration. Physical examination of the lesion revealed a 3-mm, firm, white, dome-shaped papule. Clinical features were most consistent with a benign acquired milium. The patient desired removal for cosmesis. The area was cleaned with an alcohol swab, the surface of the milium was nicked with a No. 11 blade (Figure, A), and then tips of nontoothed Adson forceps were used to gently secure and pinch the base of the papule (Figure, B). The intact cyst was quickly and effortlessly expressed through the epidermal nick. The patient tolerated the procedure well, experiencing minimal pain and bleeding.

Histologically, milia represent infundibular keratin-filled cysts lined with stratified squamous epithelial tissue that contains a granular cell layer. These lesions are classified as primary or secondary; the former represent spontaneous occurrence, and the latter are associated with medications, trauma, or genodermatoses.² Multiple milia are associated with conditions such as Bazex-Dupré-Christol syndrome, Rombo syndrome, Brooke-Spiegler syndrome, oro-facial-digital syndrome type I, atrichia with papular lesions, pachyonychia congenita type 2, basal cell nevus syndrome, basaloid follicular hamartoma syndrome, and hereditary vitamin D–dependent rickets type 2.^5-9 The most common subtype seen in clinical practice includes benign primary milia, which tends to favor the cheeks and eyelids.²

Although these lesions are benign, many patients seek extraction for cosmesis. Milia extraction is a common procedure performed in dermatology clinical practice. Proposed extraction techniques using destructive methods include electrocautery, electrodesiccation, and laser therapy, and manual methods include nicking the surface of the lesion with a scalpel blade, needle, or stylet and then applying tangential pressure with a curette, comedone extractor, paper clip, cotton-tipped applicator, tongue blade, or hypodermic needle.^1-4 Topical retinoids have been proposed as treatment of multiple milia.¹⁰ Many of these techniques do not use equipment common to clinical practice, or they fail to stabilize milia in sensitive areas, which makes extraction challenging. We describe a case with a new manual technique that successfully extracts milia in an efficient and safe manner.

To the Editor:

Several techniques can be used to destroy milia including electrocautery, electrodesiccation, and laser therapy. Manual extraction of milia uses a scalpel blade, needle, or stylet followed by the application of pressure to the lesion with a curette, comedone extractor, paper clip, cotton-tipped applicator, tongue blade, or hypodermic needle.^1-4 Many of these techniques fail to stabilize milia, particularly in sensitive areas such as around the eyes or mouth, which can make extraction challenging, inefficient, and painful for the patient. We report a novel technique that quickly and effectively removes milia with equipment commonly used in the practice of clinical dermatology.

A 74-year-old woman presented with an asymptomatic papule on the right lower vermilion border of several years' duration. Physical examination of the lesion revealed a 3-mm, firm, white, dome-shaped papule. Clinical features were most consistent with a benign acquired milium. The patient desired removal for cosmesis. The area was cleaned with an alcohol swab, the surface of the milium was nicked with a No. 11 blade (Figure, A), and then tips of nontoothed Adson forceps were used to gently secure and pinch the base of the papule (Figure, B). The intact cyst was quickly and effortlessly expressed through the epidermal nick. The patient tolerated the procedure well, experiencing minimal pain and bleeding.

Histologically, milia represent infundibular keratin-filled cysts lined with stratified squamous epithelial tissue that contains a granular cell layer. These lesions are classified as primary or secondary; the former represent spontaneous occurrence, and the latter are associated with medications, trauma, or genodermatoses.² Multiple milia are associated with conditions such as Bazex-Dupré-Christol syndrome, Rombo syndrome, Brooke-Spiegler syndrome, oro-facial-digital syndrome type I, atrichia with papular lesions, pachyonychia congenita type 2, basal cell nevus syndrome, basaloid follicular hamartoma syndrome, and hereditary vitamin D–dependent rickets type 2.^5-9 The most common subtype seen in clinical practice includes benign primary milia, which tends to favor the cheeks and eyelids.²

Although these lesions are benign, many patients seek extraction for cosmesis. Milia extraction is a common procedure performed in dermatology clinical practice. Proposed extraction techniques using destructive methods include electrocautery, electrodesiccation, and laser therapy, and manual methods include nicking the surface of the lesion with a scalpel blade, needle, or stylet and then applying tangential pressure with a curette, comedone extractor, paper clip, cotton-tipped applicator, tongue blade, or hypodermic needle.^1-4 Topical retinoids have been proposed as treatment of multiple milia.¹⁰ Many of these techniques do not use equipment common to clinical practice, or they fail to stabilize milia in sensitive areas, which makes extraction challenging. We describe a case with a new manual technique that successfully extracts milia in an efficient and safe manner.

To the Editor:

Several techniques can be used to destroy milia including electrocautery, electrodesiccation, and laser therapy. Manual extraction of milia uses a scalpel blade, needle, or stylet followed by the application of pressure to the lesion with a curette, comedone extractor, paper clip, cotton-tipped applicator, tongue blade, or hypodermic needle.^1-4 Many of these techniques fail to stabilize milia, particularly in sensitive areas such as around the eyes or mouth, which can make extraction challenging, inefficient, and painful for the patient. We report a novel technique that quickly and effectively removes milia with equipment commonly used in the practice of clinical dermatology.

A 74-year-old woman presented with an asymptomatic papule on the right lower vermilion border of several years' duration. Physical examination of the lesion revealed a 3-mm, firm, white, dome-shaped papule. Clinical features were most consistent with a benign acquired milium. The patient desired removal for cosmesis. The area was cleaned with an alcohol swab, the surface of the milium was nicked with a No. 11 blade (Figure, A), and then tips of nontoothed Adson forceps were used to gently secure and pinch the base of the papule (Figure, B). The intact cyst was quickly and effortlessly expressed through the epidermal nick. The patient tolerated the procedure well, experiencing minimal pain and bleeding.

Histologically, milia represent infundibular keratin-filled cysts lined with stratified squamous epithelial tissue that contains a granular cell layer. These lesions are classified as primary or secondary; the former represent spontaneous occurrence, and the latter are associated with medications, trauma, or genodermatoses.² Multiple milia are associated with conditions such as Bazex-Dupré-Christol syndrome, Rombo syndrome, Brooke-Spiegler syndrome, oro-facial-digital syndrome type I, atrichia with papular lesions, pachyonychia congenita type 2, basal cell nevus syndrome, basaloid follicular hamartoma syndrome, and hereditary vitamin D–dependent rickets type 2.^5-9 The most common subtype seen in clinical practice includes benign primary milia, which tends to favor the cheeks and eyelids.²

Although these lesions are benign, many patients seek extraction for cosmesis. Milia extraction is a common procedure performed in dermatology clinical practice. Proposed extraction techniques using destructive methods include electrocautery, electrodesiccation, and laser therapy, and manual methods include nicking the surface of the lesion with a scalpel blade, needle, or stylet and then applying tangential pressure with a curette, comedone extractor, paper clip, cotton-tipped applicator, tongue blade, or hypodermic needle.^1-4 Topical retinoids have been proposed as treatment of multiple milia.¹⁰ Many of these techniques do not use equipment common to clinical practice, or they fail to stabilize milia in sensitive areas, which makes extraction challenging. We describe a case with a new manual technique that successfully extracts milia in an efficient and safe manner.

Motherhood and dermatology residency are both full-time jobs. The thought that a woman must either be superhuman to succeed at both or that success at one must come at the expense of the other is antiquated. With careful navigation and sufficient support, these two roles can complement and heighten one another. The most recent Accreditation Council for Graduate Medical Education (ACGME) report showed that nearly 60% of dermatology residents are women,¹ with most women in training being of childbearing age. One study showed that female dermatologists were most likely to have children during residency (51% of those surveyed), despite residents reporting more barriers to childbearing at this career stage.² Trainees thinking of starting a family have many considerations to navigate: timing of pregnancy, maternity leave scheduling, breastfeeding while working, and planning for childcare. For the first time in the history of the specialty, most active dermatologists in practice are women.³ Thus, the future of dermatology requires supportive policies and resources for the successful navigation of these issues by today’s trainees.

Timing of Pregnancy

Timing of pregnancy can be a source of stress to the female dermatology resident. Barriers to childbearing during residency include the perception that women who have children during residency training are less committed to their jobs; concerns of overburdening fellow residents; and fear that residency may need to be extended, thereby delaying the ability to sit for the board examination.² However, the potential increased risk for infertility in delaying pregnancy adds to the stress of pregnancy planning. A 2016 survey of female physicians (N=327) showed that 24.1% of respondents who had attempted conception were diagnosed with infertility, with an average age at diagnosis of 33.7 years.⁴ This is higher than the national average, with the Centers for Disease Control and Prevention reporting that approximately 19% of women aged 15 to 49 years with no prior births experience infertility.⁵ In a 1992 survey of female physician residents (N=373) who gave birth during residency, 32% indicated that they would not recommend the experience to others; of the 68% who would recommend the experience, one-third encouraged timing delivery to occur in the last 2 months of residency due to benefits of continued insurance coverage, a decrease in clinic responsibilities, and the potential for extended maternity leave during hiatus between jobs.⁶ Although this may be a good strategy, studying and sitting for board examinations while caring for a newborn right after graduation may be overly difficult for some. The first year of residency was perceived as the most stressful time to be pregnant, with each subsequent year being less problematic.⁶ Planning pregnancy for delivery near the end of the second year and beginning of the third year of dermatology residency may be a reasonable choice.

Maternity Leave

The Family and Medical Leave Act entitles eligible employees of covered employers to take unpaid, job-protected leave, with 12 workweeks of leave in a 12-month period for the birth of a child and to care for the newborn child within 1 year of birth.⁷ The actual length of maternity leave taken by most surveyed female dermatologists (n=96) is shorter: 25% (24/96) took less than 4 weeks, 42.7% (41/96) took 4 to 8 weeks, 25% (24/96) took 9 to 12 weeks, and 7.3% (7/96) were able to take more than 12 weeks of maternity leave.²

The American Board of Dermatology implemented a new Resident Leave policy that went into effect July 1, 2021, stipulating that, within certain parameters, time spent away from training for family and parental leave would not exhaust vacation time or require an extension in training. Under this policy, absence from training exceeding 8 weeks (6 weeks leave, plus 2 weeks of vacation) in a given year should be approved only under exceptional circumstances and may necessitate additional training time to ensure that competency requirements are met.⁸ Although this policy is a step in the right direction, institutional policies still may vary. Dermatology residents planning to start a family during training should consider their plans for fellowship, as taking an extended maternity leave beyond 8 weeks may jeopardize a July fellowship start date.

Lactation and Residency

The American Academy of Pediatrics recommends exclusive breastfeeding for approximately 6 months, with continuation of breastfeeding for 1 year or longer as mutually desired by the mother and infant.⁹ Successful lactation and achieving breastfeeding goals can be difficult during medical training. A national cross-sectional survey of female residents (N=312) showed that the median total time of breastfeeding and pumping was 9 months, with 74% continuing after 6 months and 13% continuing past 12 months. Of those surveyed, 73% reported residency limited their ability to lactate, and 37% stopped prior to their desired goal.¹⁰ As of July 1, 2020, the ACGME requires that residency programs and sponsoring institutions provide clean and private facilities for lactation that have refrigeration capabilities, with proximity appropriate for safe patient care.¹¹ There has been a call to dermatology program leadership to support breastfeeding residents by providing sufficient time and space to pump; a breastfeeding resident will need a 20- to 30-minute break to express milk approximately every 3 hours during the work day.¹² One innovative initiative to meet the ACGME lactation requirement reported by the Kansas University Medical Center Graduate Medical Education program (Kansas City, Kansas) was the purchase of wearable breast pumps to loan to residents. The benefits of wearable breast pumps are that they are discreet and can allow mothers to express milk inconspicuously while working, can increase milk supply, require less set up and expression time than traditional pumps, and can allow the mother to manage time more efficiently.¹³ Breastfeeding plans and goals should be discussed with program leadership before return from leave to strategize and anticipate gaps in clinic scheduling to accommodate the lactating resident.

Planning for Childcare

Resident hours can be long and erratic, making choices for childcare difficult. In one survey of female residents, 61% of married or partnered respondents (n=447) were delaying childbearing, and 46% cited lack of access to childcare as a reason.¹⁴ Not all dermatology residents are fortunate enough to match to a program near family, but close family support can be an undeniable asset during childrearing and should be weighed heavily when ranking programs. Options for childcare include relying on a stay-at-home spouse or other family member, a live-in or live-out nanny, part-time babysitters, and daycare. It is crucial to have multiple layers and back-up options for childcare available at any given time when working as a resident. Even with a child enrolled in a full-time daycare and a live-in nanny, a daycare closure due to a COVID-19 exposure or sudden medical emergency in the nanny can still leave unpredicted holes in your childcare plan, leaving the resident to potentially miss work to fill the gap. A survey of residents at one institution showed that the most common backup childcare plan for situations in which either the child or the regular caregiver is ill is for the nontrainee parent or spouse to stay home (45%; n=101), with 25% of respondents staying home to care for a sick child themselves, which clearly has an impact on the hospital. The article proposed implementation of on-site or near-site childcare for residents with extended hours or a 24-hour emergency drop-in availability.¹⁵ One institution reported success with the development of a departmentally funded childcare supplementation stipend offered to residents to support daycare costs during the first 6 months of a baby’s life.¹⁶

Final Thoughts

Due to the competitiveness of the field, dermatology residents are by nature high performing and academically successful. For a high achiever, the idea of potentially disappointing faculty and colleagues by starting a family during residency can be guilt inducing. Concerns about one’s ability to adequately study the breadth of dermatology while simultaneously raising a child can be distressing; however, there are many ways in which motherhood can hone skills to become a better dermatology resident. Through motherhood one can enhance time management skills, increase efficiency, and improve rapport with pediatric patients and trust with their parents/guardians. A dermatology resident may be her own harshest critic, but it is time that the future generation of dermatologists become their own greatest advocates for establishing supportive policies and resources for the successful navigation of motherhood and dermatology residency.

Motherhood and dermatology residency are both full-time jobs. The thought that a woman must either be superhuman to succeed at both or that success at one must come at the expense of the other is antiquated. With careful navigation and sufficient support, these two roles can complement and heighten one another. The most recent Accreditation Council for Graduate Medical Education (ACGME) report showed that nearly 60% of dermatology residents are women,¹ with most women in training being of childbearing age. One study showed that female dermatologists were most likely to have children during residency (51% of those surveyed), despite residents reporting more barriers to childbearing at this career stage.² Trainees thinking of starting a family have many considerations to navigate: timing of pregnancy, maternity leave scheduling, breastfeeding while working, and planning for childcare. For the first time in the history of the specialty, most active dermatologists in practice are women.³ Thus, the future of dermatology requires supportive policies and resources for the successful navigation of these issues by today’s trainees.

Timing of Pregnancy

Timing of pregnancy can be a source of stress to the female dermatology resident. Barriers to childbearing during residency include the perception that women who have children during residency training are less committed to their jobs; concerns of overburdening fellow residents; and fear that residency may need to be extended, thereby delaying the ability to sit for the board examination.² However, the potential increased risk for infertility in delaying pregnancy adds to the stress of pregnancy planning. A 2016 survey of female physicians (N=327) showed that 24.1% of respondents who had attempted conception were diagnosed with infertility, with an average age at diagnosis of 33.7 years.⁴ This is higher than the national average, with the Centers for Disease Control and Prevention reporting that approximately 19% of women aged 15 to 49 years with no prior births experience infertility.⁵ In a 1992 survey of female physician residents (N=373) who gave birth during residency, 32% indicated that they would not recommend the experience to others; of the 68% who would recommend the experience, one-third encouraged timing delivery to occur in the last 2 months of residency due to benefits of continued insurance coverage, a decrease in clinic responsibilities, and the potential for extended maternity leave during hiatus between jobs.⁶ Although this may be a good strategy, studying and sitting for board examinations while caring for a newborn right after graduation may be overly difficult for some. The first year of residency was perceived as the most stressful time to be pregnant, with each subsequent year being less problematic.⁶ Planning pregnancy for delivery near the end of the second year and beginning of the third year of dermatology residency may be a reasonable choice.

Maternity Leave

The Family and Medical Leave Act entitles eligible employees of covered employers to take unpaid, job-protected leave, with 12 workweeks of leave in a 12-month period for the birth of a child and to care for the newborn child within 1 year of birth.⁷ The actual length of maternity leave taken by most surveyed female dermatologists (n=96) is shorter: 25% (24/96) took less than 4 weeks, 42.7% (41/96) took 4 to 8 weeks, 25% (24/96) took 9 to 12 weeks, and 7.3% (7/96) were able to take more than 12 weeks of maternity leave.²

The American Board of Dermatology implemented a new Resident Leave policy that went into effect July 1, 2021, stipulating that, within certain parameters, time spent away from training for family and parental leave would not exhaust vacation time or require an extension in training. Under this policy, absence from training exceeding 8 weeks (6 weeks leave, plus 2 weeks of vacation) in a given year should be approved only under exceptional circumstances and may necessitate additional training time to ensure that competency requirements are met.⁸ Although this policy is a step in the right direction, institutional policies still may vary. Dermatology residents planning to start a family during training should consider their plans for fellowship, as taking an extended maternity leave beyond 8 weeks may jeopardize a July fellowship start date.

Lactation and Residency

The American Academy of Pediatrics recommends exclusive breastfeeding for approximately 6 months, with continuation of breastfeeding for 1 year or longer as mutually desired by the mother and infant.⁹ Successful lactation and achieving breastfeeding goals can be difficult during medical training. A national cross-sectional survey of female residents (N=312) showed that the median total time of breastfeeding and pumping was 9 months, with 74% continuing after 6 months and 13% continuing past 12 months. Of those surveyed, 73% reported residency limited their ability to lactate, and 37% stopped prior to their desired goal.¹⁰ As of July 1, 2020, the ACGME requires that residency programs and sponsoring institutions provide clean and private facilities for lactation that have refrigeration capabilities, with proximity appropriate for safe patient care.¹¹ There has been a call to dermatology program leadership to support breastfeeding residents by providing sufficient time and space to pump; a breastfeeding resident will need a 20- to 30-minute break to express milk approximately every 3 hours during the work day.¹² One innovative initiative to meet the ACGME lactation requirement reported by the Kansas University Medical Center Graduate Medical Education program (Kansas City, Kansas) was the purchase of wearable breast pumps to loan to residents. The benefits of wearable breast pumps are that they are discreet and can allow mothers to express milk inconspicuously while working, can increase milk supply, require less set up and expression time than traditional pumps, and can allow the mother to manage time more efficiently.¹³ Breastfeeding plans and goals should be discussed with program leadership before return from leave to strategize and anticipate gaps in clinic scheduling to accommodate the lactating resident.

Planning for Childcare

Resident hours can be long and erratic, making choices for childcare difficult. In one survey of female residents, 61% of married or partnered respondents (n=447) were delaying childbearing, and 46% cited lack of access to childcare as a reason.¹⁴ Not all dermatology residents are fortunate enough to match to a program near family, but close family support can be an undeniable asset during childrearing and should be weighed heavily when ranking programs. Options for childcare include relying on a stay-at-home spouse or other family member, a live-in or live-out nanny, part-time babysitters, and daycare. It is crucial to have multiple layers and back-up options for childcare available at any given time when working as a resident. Even with a child enrolled in a full-time daycare and a live-in nanny, a daycare closure due to a COVID-19 exposure or sudden medical emergency in the nanny can still leave unpredicted holes in your childcare plan, leaving the resident to potentially miss work to fill the gap. A survey of residents at one institution showed that the most common backup childcare plan for situations in which either the child or the regular caregiver is ill is for the nontrainee parent or spouse to stay home (45%; n=101), with 25% of respondents staying home to care for a sick child themselves, which clearly has an impact on the hospital. The article proposed implementation of on-site or near-site childcare for residents with extended hours or a 24-hour emergency drop-in availability.¹⁵ One institution reported success with the development of a departmentally funded childcare supplementation stipend offered to residents to support daycare costs during the first 6 months of a baby’s life.¹⁶

Final Thoughts

Due to the competitiveness of the field, dermatology residents are by nature high performing and academically successful. For a high achiever, the idea of potentially disappointing faculty and colleagues by starting a family during residency can be guilt inducing. Concerns about one’s ability to adequately study the breadth of dermatology while simultaneously raising a child can be distressing; however, there are many ways in which motherhood can hone skills to become a better dermatology resident. Through motherhood one can enhance time management skills, increase efficiency, and improve rapport with pediatric patients and trust with their parents/guardians. A dermatology resident may be her own harshest critic, but it is time that the future generation of dermatologists become their own greatest advocates for establishing supportive policies and resources for the successful navigation of motherhood and dermatology residency.

Motherhood and dermatology residency are both full-time jobs. The thought that a woman must either be superhuman to succeed at both or that success at one must come at the expense of the other is antiquated. With careful navigation and sufficient support, these two roles can complement and heighten one another. The most recent Accreditation Council for Graduate Medical Education (ACGME) report showed that nearly 60% of dermatology residents are women,¹ with most women in training being of childbearing age. One study showed that female dermatologists were most likely to have children during residency (51% of those surveyed), despite residents reporting more barriers to childbearing at this career stage.² Trainees thinking of starting a family have many considerations to navigate: timing of pregnancy, maternity leave scheduling, breastfeeding while working, and planning for childcare. For the first time in the history of the specialty, most active dermatologists in practice are women.³ Thus, the future of dermatology requires supportive policies and resources for the successful navigation of these issues by today’s trainees.

Timing of Pregnancy

Timing of pregnancy can be a source of stress to the female dermatology resident. Barriers to childbearing during residency include the perception that women who have children during residency training are less committed to their jobs; concerns of overburdening fellow residents; and fear that residency may need to be extended, thereby delaying the ability to sit for the board examination.² However, the potential increased risk for infertility in delaying pregnancy adds to the stress of pregnancy planning. A 2016 survey of female physicians (N=327) showed that 24.1% of respondents who had attempted conception were diagnosed with infertility, with an average age at diagnosis of 33.7 years.⁴ This is higher than the national average, with the Centers for Disease Control and Prevention reporting that approximately 19% of women aged 15 to 49 years with no prior births experience infertility.⁵ In a 1992 survey of female physician residents (N=373) who gave birth during residency, 32% indicated that they would not recommend the experience to others; of the 68% who would recommend the experience, one-third encouraged timing delivery to occur in the last 2 months of residency due to benefits of continued insurance coverage, a decrease in clinic responsibilities, and the potential for extended maternity leave during hiatus between jobs.⁶ Although this may be a good strategy, studying and sitting for board examinations while caring for a newborn right after graduation may be overly difficult for some. The first year of residency was perceived as the most stressful time to be pregnant, with each subsequent year being less problematic.⁶ Planning pregnancy for delivery near the end of the second year and beginning of the third year of dermatology residency may be a reasonable choice.

Maternity Leave

The Family and Medical Leave Act entitles eligible employees of covered employers to take unpaid, job-protected leave, with 12 workweeks of leave in a 12-month period for the birth of a child and to care for the newborn child within 1 year of birth.⁷ The actual length of maternity leave taken by most surveyed female dermatologists (n=96) is shorter: 25% (24/96) took less than 4 weeks, 42.7% (41/96) took 4 to 8 weeks, 25% (24/96) took 9 to 12 weeks, and 7.3% (7/96) were able to take more than 12 weeks of maternity leave.²

The American Board of Dermatology implemented a new Resident Leave policy that went into effect July 1, 2021, stipulating that, within certain parameters, time spent away from training for family and parental leave would not exhaust vacation time or require an extension in training. Under this policy, absence from training exceeding 8 weeks (6 weeks leave, plus 2 weeks of vacation) in a given year should be approved only under exceptional circumstances and may necessitate additional training time to ensure that competency requirements are met.⁸ Although this policy is a step in the right direction, institutional policies still may vary. Dermatology residents planning to start a family during training should consider their plans for fellowship, as taking an extended maternity leave beyond 8 weeks may jeopardize a July fellowship start date.

Lactation and Residency

The American Academy of Pediatrics recommends exclusive breastfeeding for approximately 6 months, with continuation of breastfeeding for 1 year or longer as mutually desired by the mother and infant.⁹ Successful lactation and achieving breastfeeding goals can be difficult during medical training. A national cross-sectional survey of female residents (N=312) showed that the median total time of breastfeeding and pumping was 9 months, with 74% continuing after 6 months and 13% continuing past 12 months. Of those surveyed, 73% reported residency limited their ability to lactate, and 37% stopped prior to their desired goal.¹⁰ As of July 1, 2020, the ACGME requires that residency programs and sponsoring institutions provide clean and private facilities for lactation that have refrigeration capabilities, with proximity appropriate for safe patient care.¹¹ There has been a call to dermatology program leadership to support breastfeeding residents by providing sufficient time and space to pump; a breastfeeding resident will need a 20- to 30-minute break to express milk approximately every 3 hours during the work day.¹² One innovative initiative to meet the ACGME lactation requirement reported by the Kansas University Medical Center Graduate Medical Education program (Kansas City, Kansas) was the purchase of wearable breast pumps to loan to residents. The benefits of wearable breast pumps are that they are discreet and can allow mothers to express milk inconspicuously while working, can increase milk supply, require less set up and expression time than traditional pumps, and can allow the mother to manage time more efficiently.¹³ Breastfeeding plans and goals should be discussed with program leadership before return from leave to strategize and anticipate gaps in clinic scheduling to accommodate the lactating resident.

Planning for Childcare

Resident hours can be long and erratic, making choices for childcare difficult. In one survey of female residents, 61% of married or partnered respondents (n=447) were delaying childbearing, and 46% cited lack of access to childcare as a reason.¹⁴ Not all dermatology residents are fortunate enough to match to a program near family, but close family support can be an undeniable asset during childrearing and should be weighed heavily when ranking programs. Options for childcare include relying on a stay-at-home spouse or other family member, a live-in or live-out nanny, part-time babysitters, and daycare. It is crucial to have multiple layers and back-up options for childcare available at any given time when working as a resident. Even with a child enrolled in a full-time daycare and a live-in nanny, a daycare closure due to a COVID-19 exposure or sudden medical emergency in the nanny can still leave unpredicted holes in your childcare plan, leaving the resident to potentially miss work to fill the gap. A survey of residents at one institution showed that the most common backup childcare plan for situations in which either the child or the regular caregiver is ill is for the nontrainee parent or spouse to stay home (45%; n=101), with 25% of respondents staying home to care for a sick child themselves, which clearly has an impact on the hospital. The article proposed implementation of on-site or near-site childcare for residents with extended hours or a 24-hour emergency drop-in availability.¹⁵ One institution reported success with the development of a departmentally funded childcare supplementation stipend offered to residents to support daycare costs during the first 6 months of a baby’s life.¹⁶

Final Thoughts

Due to the competitiveness of the field, dermatology residents are by nature high performing and academically successful. For a high achiever, the idea of potentially disappointing faculty and colleagues by starting a family during residency can be guilt inducing. Concerns about one’s ability to adequately study the breadth of dermatology while simultaneously raising a child can be distressing; however, there are many ways in which motherhood can hone skills to become a better dermatology resident. Through motherhood one can enhance time management skills, increase efficiency, and improve rapport with pediatric patients and trust with their parents/guardians. A dermatology resident may be her own harshest critic, but it is time that the future generation of dermatologists become their own greatest advocates for establishing supportive policies and resources for the successful navigation of motherhood and dermatology residency.

To the Editor:

A 58-year-old man with a pigmented lesion on the left lower eyelid was referred to the oculoplastic clinic by an outside ophthalmologist. The patient had noticed the lesion growing over the course of the last 4 to 5 months. He reported scant amounts of blood and discharge coming from the nose and left eye the week prior, which persisted for 3 days. He had no associated pain or discomfort. A slit-lamp examination revealed a pigmented left lower eyelid lesion measuring 20×15 mm with telangiectasia and an eyelid margin abnormality with no palpable lymphadenopathy. The patient was diagnosed with clinical stage T3N0M0 malignant conjunctival melanoma of the left eyelid based on the American Joint Committee on Cancer classification. It is thought to have originated from conjunctival primary acquired melanosis (PAM). The T3 stage is defined as malignant melanoma with local invasion; the lesion involved the eyelid and puncta as well as canalicular portions of the lacrimal drainage system.¹ The bloody discharge was attributed to the involvement of the canalicular system, which drains tears from the eye to the nose. Melanomas can bleed, so any bloody discharge from the eye also will come through the ipsilateral nasal passage. Oncology evaluated the lesion to help determine the stage, and they found no lymph node involvement or brain, neck, chest, abdominal, or pelvic metastasis by computed tomography and magnetic resonance imaging. Sentinel lymph node biopsy was discussed with head and neck oncology specialists and was ultimately not performed per the recommendation from the Head and Neck Oncology Board; it is not a common modality for managing conjunctival melanoma because it has not been shown to alter morbidity and mortality.

The entire eyelid from the medial canthus to the lateral canthus was removed without touching the pigmented mass to ensure a “no-touch” technique removal of the mass. The no-touch technique primarily is utilized to decrease the likelihood of instrumental seeding of healthy tissues or the vascular system.² This technique focuses on preventing any direct manipulation of the tumor and avoiding an incisional biopsy as well as removal of the tumor en bloc. The margins were cutaneous—3 mm lateral to the lateral canthus, 5 mm below the lid margin, and 3 mm medial to the medial canthus—with dissection of the medial tissue from the orbital rim and lacrimal sac fossa. The lacrimal sac and lower canaliculus were then resected. The conjunctiva 5 mm inferior to the pigmented mass and the entire palpebral conjunctiva was resected to the inferior fornix across the entire palpebral conjunctiva of the lower eyelid (Figure). The eyelid and lacrimal portions were removed as a unit. Essentially, the entire lower eyelid (full thickness), including the lateral canthus, medial canthus, canaliculus, and lacrimal sac, were removed en bloc. The final tumor staging after tissue evaluation by pathology and systemic evaluation by oncology was pT3N0bM0.

A tarsoconjunctival (Hughes) flap from the upper eyelid was used to reconstruct the posterior lamella (tarsus/conjunctiva) of the lower eyelid, and a full-thickness skin graft harvested from the ipsilateral upper eyelid was used to reconstruct the anterior lamella (skin) of the lower eyelid. The reconstruction site was allowed to heal for 4 weeks before severing the tarsoconjunctival graft to allow the separation of the upper and lower eyelids. Adjunctive topical ophthalmic chemotherapy (mitomycin C 0.04%) was started 4 weeks after the last surgery. The medication was applied 4 times daily for 1 week and restarted after the conjunctival erythema and injection subsided, which was approximately 2.5 weeks, on average. The regimen of applying the medication (1 week on and 2.5 weeks off) was completed for 4 cycles. At 1 year follow-up after his diagnosis, the patient was without local recurrence or evidence of systemic metastasis. We plan to have him continue ophthalmic and oncologic evaluation every 3 to 4 months for the next 24 months, and then every 6 months for years 2 through 5.

Ocular melanoma can be further divided into uveal and conjunctival types, both arising from the respective tissue. Melanoma of the conjunctiva commonly arises from PAM with atypia, which is an acquired conjunctival pigmented lesion similar to a skin nevus that has the potential to become dysplastic. In a genetic analysis of 78 conjunctival melanomas, BRAF mutations were identified in 29% (23/78) of tumors, and NRAS mutations were detected in 18% (14/78) of tumors³; however, in our case, there were no BRAF or NRAS mutations detected. In a study of 84,836 cases that included a diagnosis of melanoma, ocular melanoma comprised 5.2% of melanomas, with cutaneous, mucosal, and unknown primary sites totaling the remaining percentage of melanomas. Of 4522 patients with ocular melanomas, 85% had uveal melanomas; 4.8% had conjunctival melanoma; and 10.2% were classified as other—comprised of cornea, not otherwise specified (NOS); retina; lacrimal gland; orbit, NOS; overlapping lesion of the eye; and eye, NOS.⁴ Melanomas of the uvea, including the ciliary body, choroid, and iris, result from a notably different pathogenesis than conjunctival melanoma, with the former being primarily associated with GNAQ and GNA mutations.³ Ciliary body and choroidal melanomas each have a different pathogenesis for occurrence, with choroidal melanoma being mostly from metastasis and ciliary body melanoma from mutations or metastasis.

Pigmented lesions on the conjunctiva or sclera arise from either melanocytes or nonmelanocytes and have a diverse differential diagnosis, including congenital melanosis, conjunctival nevi, PAM or secondary acquired melanosis, or conjunctival melanoma. The diagnosis of uveal melanoma should be based on fundoscopic examination by an experienced clinician. Uveal melanoma is unlike most other cancers in that diagnosis can be by clinical fundoscopic examination alone. Imaging studies such as ultrasound and fluorescein angiography can be performed for prognostication and characterization. Fine needle aspiration biopsy for molecular analysis is becoming more routine, but the results rarely affect the plan of care. Primary treatment of uveal melanoma should strive to preserve vision and prevent metastasis; however, a primary modality has yet to show notable results in decreasing distant disease spread or overall survival. Treatment of the primary tumor should involve consideration of tumor size, location, health of the patient, and patient preference.^1,5

For patients with melanoma arising from the conjunctiva, initial management should focus on local disease control, including wide local excision to avoid seeding, supplemented with cryotherapy and alcohol epitheliectomy to the cornea to ensure local tumor extinction.^2,6 Techniques including enucleation and orbital exenteration historically have been used for treatment of extensive disease, but this approach has not been associated with improvement in mortality and is a cause of notable morbidity.^7,8 Sentinel lymph node biopsy has an established role in the management of cutaneous melanoma, but its use in the setting of conjunctival melanoma is controversial, with studies showing that up to 50% of patients with local recurrence can develop distant metastasis with no evidence of regional lymph node involvement.^9,10 When the tumor is present at the surgical margins or in the case that lesions cannot be fully excised, adjuvant therapy may improve long-term control and prevent recurrence following surgical intervention. Mitomycin C 0.04% is the most commonly used topical chemotherapy agent because it has an established role in the treatment of PAM, but it remains adjuvant therapy for conjunctival melanoma due to the relatively poor outcomes when it is used for primary therapy.¹¹

In one study, recurrence rates for conjunctival melanoma were 26%, 51%, and 65% at 5, 10, and 15 years, respectively.¹² Risk factors for recurrence include increased tumor thickness, incomplete excision, positive margins, surgical excision without adjuvant therapy, and nonlimbal location.¹³ A multivariate analysis of 150 patients showed that the melanoma location not touching the limbus (P=.01) and pathologic evidence of tumor to the lateral margin (P=.02) were related to tumor recurrence, with relative risks (IQR) of 2.3 (1.2-4.6) and 2.9 (1.2-7.1), respectively. Careful surgical planning using wide microsurgical excisional biopsy emphasizing a no-touch technique as well as supplemental alcohol therapy for the cornea and conjunctiva is advised.¹²

To the Editor:

A 58-year-old man with a pigmented lesion on the left lower eyelid was referred to the oculoplastic clinic by an outside ophthalmologist. The patient had noticed the lesion growing over the course of the last 4 to 5 months. He reported scant amounts of blood and discharge coming from the nose and left eye the week prior, which persisted for 3 days. He had no associated pain or discomfort. A slit-lamp examination revealed a pigmented left lower eyelid lesion measuring 20×15 mm with telangiectasia and an eyelid margin abnormality with no palpable lymphadenopathy. The patient was diagnosed with clinical stage T3N0M0 malignant conjunctival melanoma of the left eyelid based on the American Joint Committee on Cancer classification. It is thought to have originated from conjunctival primary acquired melanosis (PAM). The T3 stage is defined as malignant melanoma with local invasion; the lesion involved the eyelid and puncta as well as canalicular portions of the lacrimal drainage system.¹ The bloody discharge was attributed to the involvement of the canalicular system, which drains tears from the eye to the nose. Melanomas can bleed, so any bloody discharge from the eye also will come through the ipsilateral nasal passage. Oncology evaluated the lesion to help determine the stage, and they found no lymph node involvement or brain, neck, chest, abdominal, or pelvic metastasis by computed tomography and magnetic resonance imaging. Sentinel lymph node biopsy was discussed with head and neck oncology specialists and was ultimately not performed per the recommendation from the Head and Neck Oncology Board; it is not a common modality for managing conjunctival melanoma because it has not been shown to alter morbidity and mortality.

The entire eyelid from the medial canthus to the lateral canthus was removed without touching the pigmented mass to ensure a “no-touch” technique removal of the mass. The no-touch technique primarily is utilized to decrease the likelihood of instrumental seeding of healthy tissues or the vascular system.² This technique focuses on preventing any direct manipulation of the tumor and avoiding an incisional biopsy as well as removal of the tumor en bloc. The margins were cutaneous—3 mm lateral to the lateral canthus, 5 mm below the lid margin, and 3 mm medial to the medial canthus—with dissection of the medial tissue from the orbital rim and lacrimal sac fossa. The lacrimal sac and lower canaliculus were then resected. The conjunctiva 5 mm inferior to the pigmented mass and the entire palpebral conjunctiva was resected to the inferior fornix across the entire palpebral conjunctiva of the lower eyelid (Figure). The eyelid and lacrimal portions were removed as a unit. Essentially, the entire lower eyelid (full thickness), including the lateral canthus, medial canthus, canaliculus, and lacrimal sac, were removed en bloc. The final tumor staging after tissue evaluation by pathology and systemic evaluation by oncology was pT3N0bM0.

A tarsoconjunctival (Hughes) flap from the upper eyelid was used to reconstruct the posterior lamella (tarsus/conjunctiva) of the lower eyelid, and a full-thickness skin graft harvested from the ipsilateral upper eyelid was used to reconstruct the anterior lamella (skin) of the lower eyelid. The reconstruction site was allowed to heal for 4 weeks before severing the tarsoconjunctival graft to allow the separation of the upper and lower eyelids. Adjunctive topical ophthalmic chemotherapy (mitomycin C 0.04%) was started 4 weeks after the last surgery. The medication was applied 4 times daily for 1 week and restarted after the conjunctival erythema and injection subsided, which was approximately 2.5 weeks, on average. The regimen of applying the medication (1 week on and 2.5 weeks off) was completed for 4 cycles. At 1 year follow-up after his diagnosis, the patient was without local recurrence or evidence of systemic metastasis. We plan to have him continue ophthalmic and oncologic evaluation every 3 to 4 months for the next 24 months, and then every 6 months for years 2 through 5.

Ocular melanoma can be further divided into uveal and conjunctival types, both arising from the respective tissue. Melanoma of the conjunctiva commonly arises from PAM with atypia, which is an acquired conjunctival pigmented lesion similar to a skin nevus that has the potential to become dysplastic. In a genetic analysis of 78 conjunctival melanomas, BRAF mutations were identified in 29% (23/78) of tumors, and NRAS mutations were detected in 18% (14/78) of tumors³; however, in our case, there were no BRAF or NRAS mutations detected. In a study of 84,836 cases that included a diagnosis of melanoma, ocular melanoma comprised 5.2% of melanomas, with cutaneous, mucosal, and unknown primary sites totaling the remaining percentage of melanomas. Of 4522 patients with ocular melanomas, 85% had uveal melanomas; 4.8% had conjunctival melanoma; and 10.2% were classified as other—comprised of cornea, not otherwise specified (NOS); retina; lacrimal gland; orbit, NOS; overlapping lesion of the eye; and eye, NOS.⁴ Melanomas of the uvea, including the ciliary body, choroid, and iris, result from a notably different pathogenesis than conjunctival melanoma, with the former being primarily associated with GNAQ and GNA mutations.³ Ciliary body and choroidal melanomas each have a different pathogenesis for occurrence, with choroidal melanoma being mostly from metastasis and ciliary body melanoma from mutations or metastasis.

Pigmented lesions on the conjunctiva or sclera arise from either melanocytes or nonmelanocytes and have a diverse differential diagnosis, including congenital melanosis, conjunctival nevi, PAM or secondary acquired melanosis, or conjunctival melanoma. The diagnosis of uveal melanoma should be based on fundoscopic examination by an experienced clinician. Uveal melanoma is unlike most other cancers in that diagnosis can be by clinical fundoscopic examination alone. Imaging studies such as ultrasound and fluorescein angiography can be performed for prognostication and characterization. Fine needle aspiration biopsy for molecular analysis is becoming more routine, but the results rarely affect the plan of care. Primary treatment of uveal melanoma should strive to preserve vision and prevent metastasis; however, a primary modality has yet to show notable results in decreasing distant disease spread or overall survival. Treatment of the primary tumor should involve consideration of tumor size, location, health of the patient, and patient preference.^1,5

For patients with melanoma arising from the conjunctiva, initial management should focus on local disease control, including wide local excision to avoid seeding, supplemented with cryotherapy and alcohol epitheliectomy to the cornea to ensure local tumor extinction.^2,6 Techniques including enucleation and orbital exenteration historically have been used for treatment of extensive disease, but this approach has not been associated with improvement in mortality and is a cause of notable morbidity.^7,8 Sentinel lymph node biopsy has an established role in the management of cutaneous melanoma, but its use in the setting of conjunctival melanoma is controversial, with studies showing that up to 50% of patients with local recurrence can develop distant metastasis with no evidence of regional lymph node involvement.^9,10 When the tumor is present at the surgical margins or in the case that lesions cannot be fully excised, adjuvant therapy may improve long-term control and prevent recurrence following surgical intervention. Mitomycin C 0.04% is the most commonly used topical chemotherapy agent because it has an established role in the treatment of PAM, but it remains adjuvant therapy for conjunctival melanoma due to the relatively poor outcomes when it is used for primary therapy.¹¹

In one study, recurrence rates for conjunctival melanoma were 26%, 51%, and 65% at 5, 10, and 15 years, respectively.¹² Risk factors for recurrence include increased tumor thickness, incomplete excision, positive margins, surgical excision without adjuvant therapy, and nonlimbal location.¹³ A multivariate analysis of 150 patients showed that the melanoma location not touching the limbus (P=.01) and pathologic evidence of tumor to the lateral margin (P=.02) were related to tumor recurrence, with relative risks (IQR) of 2.3 (1.2-4.6) and 2.9 (1.2-7.1), respectively. Careful surgical planning using wide microsurgical excisional biopsy emphasizing a no-touch technique as well as supplemental alcohol therapy for the cornea and conjunctiva is advised.¹²

To the Editor:

A 58-year-old man with a pigmented lesion on the left lower eyelid was referred to the oculoplastic clinic by an outside ophthalmologist. The patient had noticed the lesion growing over the course of the last 4 to 5 months. He reported scant amounts of blood and discharge coming from the nose and left eye the week prior, which persisted for 3 days. He had no associated pain or discomfort. A slit-lamp examination revealed a pigmented left lower eyelid lesion measuring 20×15 mm with telangiectasia and an eyelid margin abnormality with no palpable lymphadenopathy. The patient was diagnosed with clinical stage T3N0M0 malignant conjunctival melanoma of the left eyelid based on the American Joint Committee on Cancer classification. It is thought to have originated from conjunctival primary acquired melanosis (PAM). The T3 stage is defined as malignant melanoma with local invasion; the lesion involved the eyelid and puncta as well as canalicular portions of the lacrimal drainage system.¹ The bloody discharge was attributed to the involvement of the canalicular system, which drains tears from the eye to the nose. Melanomas can bleed, so any bloody discharge from the eye also will come through the ipsilateral nasal passage. Oncology evaluated the lesion to help determine the stage, and they found no lymph node involvement or brain, neck, chest, abdominal, or pelvic metastasis by computed tomography and magnetic resonance imaging. Sentinel lymph node biopsy was discussed with head and neck oncology specialists and was ultimately not performed per the recommendation from the Head and Neck Oncology Board; it is not a common modality for managing conjunctival melanoma because it has not been shown to alter morbidity and mortality.

The entire eyelid from the medial canthus to the lateral canthus was removed without touching the pigmented mass to ensure a “no-touch” technique removal of the mass. The no-touch technique primarily is utilized to decrease the likelihood of instrumental seeding of healthy tissues or the vascular system.² This technique focuses on preventing any direct manipulation of the tumor and avoiding an incisional biopsy as well as removal of the tumor en bloc. The margins were cutaneous—3 mm lateral to the lateral canthus, 5 mm below the lid margin, and 3 mm medial to the medial canthus—with dissection of the medial tissue from the orbital rim and lacrimal sac fossa. The lacrimal sac and lower canaliculus were then resected. The conjunctiva 5 mm inferior to the pigmented mass and the entire palpebral conjunctiva was resected to the inferior fornix across the entire palpebral conjunctiva of the lower eyelid (Figure). The eyelid and lacrimal portions were removed as a unit. Essentially, the entire lower eyelid (full thickness), including the lateral canthus, medial canthus, canaliculus, and lacrimal sac, were removed en bloc. The final tumor staging after tissue evaluation by pathology and systemic evaluation by oncology was pT3N0bM0.

A tarsoconjunctival (Hughes) flap from the upper eyelid was used to reconstruct the posterior lamella (tarsus/conjunctiva) of the lower eyelid, and a full-thickness skin graft harvested from the ipsilateral upper eyelid was used to reconstruct the anterior lamella (skin) of the lower eyelid. The reconstruction site was allowed to heal for 4 weeks before severing the tarsoconjunctival graft to allow the separation of the upper and lower eyelids. Adjunctive topical ophthalmic chemotherapy (mitomycin C 0.04%) was started 4 weeks after the last surgery. The medication was applied 4 times daily for 1 week and restarted after the conjunctival erythema and injection subsided, which was approximately 2.5 weeks, on average. The regimen of applying the medication (1 week on and 2.5 weeks off) was completed for 4 cycles. At 1 year follow-up after his diagnosis, the patient was without local recurrence or evidence of systemic metastasis. We plan to have him continue ophthalmic and oncologic evaluation every 3 to 4 months for the next 24 months, and then every 6 months for years 2 through 5.

Ocular melanoma can be further divided into uveal and conjunctival types, both arising from the respective tissue. Melanoma of the conjunctiva commonly arises from PAM with atypia, which is an acquired conjunctival pigmented lesion similar to a skin nevus that has the potential to become dysplastic. In a genetic analysis of 78 conjunctival melanomas, BRAF mutations were identified in 29% (23/78) of tumors, and NRAS mutations were detected in 18% (14/78) of tumors³; however, in our case, there were no BRAF or NRAS mutations detected. In a study of 84,836 cases that included a diagnosis of melanoma, ocular melanoma comprised 5.2% of melanomas, with cutaneous, mucosal, and unknown primary sites totaling the remaining percentage of melanomas. Of 4522 patients with ocular melanomas, 85% had uveal melanomas; 4.8% had conjunctival melanoma; and 10.2% were classified as other—comprised of cornea, not otherwise specified (NOS); retina; lacrimal gland; orbit, NOS; overlapping lesion of the eye; and eye, NOS.⁴ Melanomas of the uvea, including the ciliary body, choroid, and iris, result from a notably different pathogenesis than conjunctival melanoma, with the former being primarily associated with GNAQ and GNA mutations.³ Ciliary body and choroidal melanomas each have a different pathogenesis for occurrence, with choroidal melanoma being mostly from metastasis and ciliary body melanoma from mutations or metastasis.

Pigmented lesions on the conjunctiva or sclera arise from either melanocytes or nonmelanocytes and have a diverse differential diagnosis, including congenital melanosis, conjunctival nevi, PAM or secondary acquired melanosis, or conjunctival melanoma. The diagnosis of uveal melanoma should be based on fundoscopic examination by an experienced clinician. Uveal melanoma is unlike most other cancers in that diagnosis can be by clinical fundoscopic examination alone. Imaging studies such as ultrasound and fluorescein angiography can be performed for prognostication and characterization. Fine needle aspiration biopsy for molecular analysis is becoming more routine, but the results rarely affect the plan of care. Primary treatment of uveal melanoma should strive to preserve vision and prevent metastasis; however, a primary modality has yet to show notable results in decreasing distant disease spread or overall survival. Treatment of the primary tumor should involve consideration of tumor size, location, health of the patient, and patient preference.^1,5

For patients with melanoma arising from the conjunctiva, initial management should focus on local disease control, including wide local excision to avoid seeding, supplemented with cryotherapy and alcohol epitheliectomy to the cornea to ensure local tumor extinction.^2,6 Techniques including enucleation and orbital exenteration historically have been used for treatment of extensive disease, but this approach has not been associated with improvement in mortality and is a cause of notable morbidity.^7,8 Sentinel lymph node biopsy has an established role in the management of cutaneous melanoma, but its use in the setting of conjunctival melanoma is controversial, with studies showing that up to 50% of patients with local recurrence can develop distant metastasis with no evidence of regional lymph node involvement.^9,10 When the tumor is present at the surgical margins or in the case that lesions cannot be fully excised, adjuvant therapy may improve long-term control and prevent recurrence following surgical intervention. Mitomycin C 0.04% is the most commonly used topical chemotherapy agent because it has an established role in the treatment of PAM, but it remains adjuvant therapy for conjunctival melanoma due to the relatively poor outcomes when it is used for primary therapy.¹¹

In one study, recurrence rates for conjunctival melanoma were 26%, 51%, and 65% at 5, 10, and 15 years, respectively.¹² Risk factors for recurrence include increased tumor thickness, incomplete excision, positive margins, surgical excision without adjuvant therapy, and nonlimbal location.¹³ A multivariate analysis of 150 patients showed that the melanoma location not touching the limbus (P=.01) and pathologic evidence of tumor to the lateral margin (P=.02) were related to tumor recurrence, with relative risks (IQR) of 2.3 (1.2-4.6) and 2.9 (1.2-7.1), respectively. Careful surgical planning using wide microsurgical excisional biopsy emphasizing a no-touch technique as well as supplemental alcohol therapy for the cornea and conjunctiva is advised.¹²

To the Editor:

Wolf isotopic response describes the development of a skin disorder at the site of another healed and unrelated skin disease. Skin disorders presenting as isotopic responses have included inflammatory, malignant, granulomatous, and infectious processes. Discoid lupus erythematosus (DLE) is a rare isotopic response. We report a cutaneous lupus erythematosus–like isotopic response that presented at the site of a recent herpes zoster infection in a liver transplant recipient.

A 74-year-old immunocompromised woman was referred to the dermatology clinic for evaluation of a rash on the right leg. She was being treated with maintenance valganciclovir due to cytomegalovirus viremia, as well as tacrolimus, azathioprine, and prednisone following liver transplantation due to autoimmune hepatitis for 8 months prior to presentation. Eighteen days prior to the current presentation, she was clinically diagnosed with herpes zoster. As the grouped vesicles from the herpes zoster resolved, she developed pink scaly papules in the same distribution as the original vesicular eruption.

Physical examination revealed numerous erythematous, 2- to 3-mm, scaly papules that coalesced into small plaques with serous crusts; they originated above the supragluteal cleft and extended rightward in the L3 and L4 dermatomes to the right knee (Figure 1). A 3-mm punch biopsy specimen was obtained from the right anterior thigh. Histologic analysis revealed interface lymphocytic inflammation with squamatization of basal keratinocytes, basement membrane thickening, and follicular plugging by keratin (Figure 2). There was a moderately intense perivascular and periadnexal inflammatory infiltrate of mature lymphocytes with rare eosinophils within the papillary and superficial reticular dermis. There was no evidence of a viral cytopathic effect, and an immunohistochemical stain for varicella-zoster virus protein was negative. The histologic findings were suggestive of cutaneous involvement by DLE. A diagnosis of a cutaneous lupus erythematosus–like Wolf isotopic response was made, and the patient’s rash resolved with the use of triamcinolone cream 0.1% applied twice daily for 2 weeks. At 6-week follow-up, there were postinflammatory pigmentation changes at the sites of the prior rash and persistent postherpetic neuralgia. Recent antinuclear antibody screening was negative, coupled with the patient’s lack of systemic symptoms and quick resolution of rash, indicating that additional testing for systemic lupus was not warranted.

Wolf isotopic response describes the occurrence of a new skin disorder at the site of a previously healed and unrelated skin disorder. The second disease may appear within days to years after the primary disease subsides and is clearly differentiated from the isomorphic response of the Koebner phenomenon, which describes an established skin disorder appearing at a previously uninvolved anatomic site following trauma.¹ As in our case, the initial cutaneous eruption resulting in a subsequent Wolf isotopic response frequently is herpes zoster and less commonly is herpes simplex virus.² The most common reported isotopic response is a granulomatous reaction.² Rare reports of leukemic infiltration, lymphoma, lichen planus, morphea, reactive perforating collagenosis, psoriasis, discoid lupus, lichen simplex chronicus, contact dermatitis, xanthomatous changes, malignant tumors, cutaneous graft-vs-host disease, pityriasis rosea, erythema annulare centrifugum, and other infectious-based isotopic responses exist.^2-6

Our patient presented with Wolf isotopic response that histologically mimicked DLE. A PubMed search of articles indexed for MEDLINE using the terms isotopic response and lupus revealed only 3 cases of cutaneous lupus erythematosus presenting as an isotopic response in the English-language literature. One of those cases occurred in a patient with preexisting systemic lupus erythematosus, making a diagnosis of Koebner isomorphic phenomenon more appropriate than an isotopic response at the site of prior herpes zoster infection.⁷ The remaining 2 cases were clinically defined DLE lesions occurring at sites of prior infection—cutaneous leishmaniasis and herpes zoster—in patients without a prior history of cutaneous or systemic lupus erythematosus.^8,9 The latter case of DLE-like isotopic response occurring after herpes zoster infection was further complicated by local injections at the zoster site for herpes-related local pain. Injection sites are reported as a distinct nidus for Wolf isotopic response.⁹

The pathogenesis of Wolf isotopic response is unclear. Possible explanations include local interactions between persistent viral particles at prior herpes infection sites, vascular injury, neural injury, and an altered immune response.^1,5,6,10 The destruction of sensory nerve fibers by herpesviruses cause the release of neuropeptides that then modulate the local immune system and angiogenic responses.^5,6 Our patient’s immunocompromised state may have further propagated a local altered immune cell infiltrate at the site of the isotopic response. Despite its unclear etiology, Wolf isotopic response should be considered in the differential diagnosis for any patient who presents with a dermatomal eruption at the site of a prior cutaneous infection, particularly after infection with herpes zoster. Treatment with topical or intralesional corticosteroids usually suffices for inflammatory-based isotopic responses with an excellent prognosis.¹¹

We present a case of a cutaneous lupus erythematosus–like isotopic response that occurred at the site of a recent herpes zoster eruption in an immunocompromised patient without prior history of systemic or cutaneous lupus erythematosus. Clinical recognition of Wolf isotopic response is important for accurate histopathologic diagnosis and management. Continued investigation into the underlying pathogenesis should be performed to fully understand and better treat this process.

To the Editor:

Wolf isotopic response describes the development of a skin disorder at the site of another healed and unrelated skin disease. Skin disorders presenting as isotopic responses have included inflammatory, malignant, granulomatous, and infectious processes. Discoid lupus erythematosus (DLE) is a rare isotopic response. We report a cutaneous lupus erythematosus–like isotopic response that presented at the site of a recent herpes zoster infection in a liver transplant recipient.

A 74-year-old immunocompromised woman was referred to the dermatology clinic for evaluation of a rash on the right leg. She was being treated with maintenance valganciclovir due to cytomegalovirus viremia, as well as tacrolimus, azathioprine, and prednisone following liver transplantation due to autoimmune hepatitis for 8 months prior to presentation. Eighteen days prior to the current presentation, she was clinically diagnosed with herpes zoster. As the grouped vesicles from the herpes zoster resolved, she developed pink scaly papules in the same distribution as the original vesicular eruption.

Physical examination revealed numerous erythematous, 2- to 3-mm, scaly papules that coalesced into small plaques with serous crusts; they originated above the supragluteal cleft and extended rightward in the L3 and L4 dermatomes to the right knee (Figure 1). A 3-mm punch biopsy specimen was obtained from the right anterior thigh. Histologic analysis revealed interface lymphocytic inflammation with squamatization of basal keratinocytes, basement membrane thickening, and follicular plugging by keratin (Figure 2). There was a moderately intense perivascular and periadnexal inflammatory infiltrate of mature lymphocytes with rare eosinophils within the papillary and superficial reticular dermis. There was no evidence of a viral cytopathic effect, and an immunohistochemical stain for varicella-zoster virus protein was negative. The histologic findings were suggestive of cutaneous involvement by DLE. A diagnosis of a cutaneous lupus erythematosus–like Wolf isotopic response was made, and the patient’s rash resolved with the use of triamcinolone cream 0.1% applied twice daily for 2 weeks. At 6-week follow-up, there were postinflammatory pigmentation changes at the sites of the prior rash and persistent postherpetic neuralgia. Recent antinuclear antibody screening was negative, coupled with the patient’s lack of systemic symptoms and quick resolution of rash, indicating that additional testing for systemic lupus was not warranted.

Wolf isotopic response describes the occurrence of a new skin disorder at the site of a previously healed and unrelated skin disorder. The second disease may appear within days to years after the primary disease subsides and is clearly differentiated from the isomorphic response of the Koebner phenomenon, which describes an established skin disorder appearing at a previously uninvolved anatomic site following trauma.¹ As in our case, the initial cutaneous eruption resulting in a subsequent Wolf isotopic response frequently is herpes zoster and less commonly is herpes simplex virus.² The most common reported isotopic response is a granulomatous reaction.² Rare reports of leukemic infiltration, lymphoma, lichen planus, morphea, reactive perforating collagenosis, psoriasis, discoid lupus, lichen simplex chronicus, contact dermatitis, xanthomatous changes, malignant tumors, cutaneous graft-vs-host disease, pityriasis rosea, erythema annulare centrifugum, and other infectious-based isotopic responses exist.^2-6

Our patient presented with Wolf isotopic response that histologically mimicked DLE. A PubMed search of articles indexed for MEDLINE using the terms isotopic response and lupus revealed only 3 cases of cutaneous lupus erythematosus presenting as an isotopic response in the English-language literature. One of those cases occurred in a patient with preexisting systemic lupus erythematosus, making a diagnosis of Koebner isomorphic phenomenon more appropriate than an isotopic response at the site of prior herpes zoster infection.⁷ The remaining 2 cases were clinically defined DLE lesions occurring at sites of prior infection—cutaneous leishmaniasis and herpes zoster—in patients without a prior history of cutaneous or systemic lupus erythematosus.^8,9 The latter case of DLE-like isotopic response occurring after herpes zoster infection was further complicated by local injections at the zoster site for herpes-related local pain. Injection sites are reported as a distinct nidus for Wolf isotopic response.⁹

The pathogenesis of Wolf isotopic response is unclear. Possible explanations include local interactions between persistent viral particles at prior herpes infection sites, vascular injury, neural injury, and an altered immune response.^1,5,6,10 The destruction of sensory nerve fibers by herpesviruses cause the release of neuropeptides that then modulate the local immune system and angiogenic responses.^5,6 Our patient’s immunocompromised state may have further propagated a local altered immune cell infiltrate at the site of the isotopic response. Despite its unclear etiology, Wolf isotopic response should be considered in the differential diagnosis for any patient who presents with a dermatomal eruption at the site of a prior cutaneous infection, particularly after infection with herpes zoster. Treatment with topical or intralesional corticosteroids usually suffices for inflammatory-based isotopic responses with an excellent prognosis.¹¹

We present a case of a cutaneous lupus erythematosus–like isotopic response that occurred at the site of a recent herpes zoster eruption in an immunocompromised patient without prior history of systemic or cutaneous lupus erythematosus. Clinical recognition of Wolf isotopic response is important for accurate histopathologic diagnosis and management. Continued investigation into the underlying pathogenesis should be performed to fully understand and better treat this process.

To the Editor:

Wolf isotopic response describes the development of a skin disorder at the site of another healed and unrelated skin disease. Skin disorders presenting as isotopic responses have included inflammatory, malignant, granulomatous, and infectious processes. Discoid lupus erythematosus (DLE) is a rare isotopic response. We report a cutaneous lupus erythematosus–like isotopic response that presented at the site of a recent herpes zoster infection in a liver transplant recipient.

A 74-year-old immunocompromised woman was referred to the dermatology clinic for evaluation of a rash on the right leg. She was being treated with maintenance valganciclovir due to cytomegalovirus viremia, as well as tacrolimus, azathioprine, and prednisone following liver transplantation due to autoimmune hepatitis for 8 months prior to presentation. Eighteen days prior to the current presentation, she was clinically diagnosed with herpes zoster. As the grouped vesicles from the herpes zoster resolved, she developed pink scaly papules in the same distribution as the original vesicular eruption.

Physical examination revealed numerous erythematous, 2- to 3-mm, scaly papules that coalesced into small plaques with serous crusts; they originated above the supragluteal cleft and extended rightward in the L3 and L4 dermatomes to the right knee (Figure 1). A 3-mm punch biopsy specimen was obtained from the right anterior thigh. Histologic analysis revealed interface lymphocytic inflammation with squamatization of basal keratinocytes, basement membrane thickening, and follicular plugging by keratin (Figure 2). There was a moderately intense perivascular and periadnexal inflammatory infiltrate of mature lymphocytes with rare eosinophils within the papillary and superficial reticular dermis. There was no evidence of a viral cytopathic effect, and an immunohistochemical stain for varicella-zoster virus protein was negative. The histologic findings were suggestive of cutaneous involvement by DLE. A diagnosis of a cutaneous lupus erythematosus–like Wolf isotopic response was made, and the patient’s rash resolved with the use of triamcinolone cream 0.1% applied twice daily for 2 weeks. At 6-week follow-up, there were postinflammatory pigmentation changes at the sites of the prior rash and persistent postherpetic neuralgia. Recent antinuclear antibody screening was negative, coupled with the patient’s lack of systemic symptoms and quick resolution of rash, indicating that additional testing for systemic lupus was not warranted.

Wolf isotopic response describes the occurrence of a new skin disorder at the site of a previously healed and unrelated skin disorder. The second disease may appear within days to years after the primary disease subsides and is clearly differentiated from the isomorphic response of the Koebner phenomenon, which describes an established skin disorder appearing at a previously uninvolved anatomic site following trauma.¹ As in our case, the initial cutaneous eruption resulting in a subsequent Wolf isotopic response frequently is herpes zoster and less commonly is herpes simplex virus.² The most common reported isotopic response is a granulomatous reaction.² Rare reports of leukemic infiltration, lymphoma, lichen planus, morphea, reactive perforating collagenosis, psoriasis, discoid lupus, lichen simplex chronicus, contact dermatitis, xanthomatous changes, malignant tumors, cutaneous graft-vs-host disease, pityriasis rosea, erythema annulare centrifugum, and other infectious-based isotopic responses exist.^2-6

Our patient presented with Wolf isotopic response that histologically mimicked DLE. A PubMed search of articles indexed for MEDLINE using the terms isotopic response and lupus revealed only 3 cases of cutaneous lupus erythematosus presenting as an isotopic response in the English-language literature. One of those cases occurred in a patient with preexisting systemic lupus erythematosus, making a diagnosis of Koebner isomorphic phenomenon more appropriate than an isotopic response at the site of prior herpes zoster infection.⁷ The remaining 2 cases were clinically defined DLE lesions occurring at sites of prior infection—cutaneous leishmaniasis and herpes zoster—in patients without a prior history of cutaneous or systemic lupus erythematosus.^8,9 The latter case of DLE-like isotopic response occurring after herpes zoster infection was further complicated by local injections at the zoster site for herpes-related local pain. Injection sites are reported as a distinct nidus for Wolf isotopic response.⁹

The pathogenesis of Wolf isotopic response is unclear. Possible explanations include local interactions between persistent viral particles at prior herpes infection sites, vascular injury, neural injury, and an altered immune response.^1,5,6,10 The destruction of sensory nerve fibers by herpesviruses cause the release of neuropeptides that then modulate the local immune system and angiogenic responses.^5,6 Our patient’s immunocompromised state may have further propagated a local altered immune cell infiltrate at the site of the isotopic response. Despite its unclear etiology, Wolf isotopic response should be considered in the differential diagnosis for any patient who presents with a dermatomal eruption at the site of a prior cutaneous infection, particularly after infection with herpes zoster. Treatment with topical or intralesional corticosteroids usually suffices for inflammatory-based isotopic responses with an excellent prognosis.¹¹

We present a case of a cutaneous lupus erythematosus–like isotopic response that occurred at the site of a recent herpes zoster eruption in an immunocompromised patient without prior history of systemic or cutaneous lupus erythematosus. Clinical recognition of Wolf isotopic response is important for accurate histopathologic diagnosis and management. Continued investigation into the underlying pathogenesis should be performed to fully understand and better treat this process.