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The Diagnosis: Epidermotropic CD8⁺ T-Cell Lymphoma

Epidermotropic CD8⁺ T-cell lymphoma is a rare aggressive form of cutaneous T-cell lymphoma (CTCL), accounting for less than 1% of all cases.¹ Since this subtype of CTCL was first described in 1999 by Berti et al,² approximately 45 cases have been reported in the literature.¹ It typically is found in elderly men and presents as disseminated or localized papules, patches, plaques, nodules, and tumors, often with central necrosis, ulceration, crusting, and hemorrhage (Figure 1).^1,3 These lesions rapidly progress and can affect any skin site, but acral accentuation and mucosal involvement are common.⁴ Due to the rapidly progressive nature of this disease, patients typically present with widespread plaque- and tumor-stage disease.³ Frequency of systemic spread is high, with metastasis to the central nervous system, lungs, and testes being most common. Lymph nodes typically are spared, helping to differentiate this form of CTCL from classic mycosis fungoides.

Diagnosis of epidermotropic CD8⁺ T-cell lymphoma is based on a combination of clinical, histopathologic, and immunohistochemical features. Histopathologic components include epidermotropism, particularly in the basal cell layer, in a pagetoid or linear pattern. A second feature is a dermal infiltrate consisting of a nodular or diffuse pattern of atypical lymphocytes that extend to the subcutaneous fat (Figure 2). All cases of epidermotropic CD8⁺ T-cell lymphoma express the CD8⁺ phenotype and most have a high Ki-67 proliferation index and are CD3, CD45RA, and/or T-cell intracellular antigen 1 positive.¹

Due to its aggressive nature, epidermotropic CD8⁺ T-cell lymphoma has a poor prognosis, with an average 5-year survival rate of 18% and median survival of 22.5 months.³ Treatment proves difficult as conventional therapies for CD4⁺ CTCL have proven ineffective for epidermotropic CD8⁺ T-cell lymphoma. Partial response has been seen with bexarotene alone and with total skin electron beam therapy combined with oral retinoids.¹

The Diagnosis: Epidermotropic CD8⁺ T-Cell Lymphoma

Epidermotropic CD8⁺ T-cell lymphoma is a rare aggressive form of cutaneous T-cell lymphoma (CTCL), accounting for less than 1% of all cases.¹ Since this subtype of CTCL was first described in 1999 by Berti et al,² approximately 45 cases have been reported in the literature.¹ It typically is found in elderly men and presents as disseminated or localized papules, patches, plaques, nodules, and tumors, often with central necrosis, ulceration, crusting, and hemorrhage (Figure 1).^1,3 These lesions rapidly progress and can affect any skin site, but acral accentuation and mucosal involvement are common.⁴ Due to the rapidly progressive nature of this disease, patients typically present with widespread plaque- and tumor-stage disease.³ Frequency of systemic spread is high, with metastasis to the central nervous system, lungs, and testes being most common. Lymph nodes typically are spared, helping to differentiate this form of CTCL from classic mycosis fungoides.

Diagnosis of epidermotropic CD8⁺ T-cell lymphoma is based on a combination of clinical, histopathologic, and immunohistochemical features. Histopathologic components include epidermotropism, particularly in the basal cell layer, in a pagetoid or linear pattern. A second feature is a dermal infiltrate consisting of a nodular or diffuse pattern of atypical lymphocytes that extend to the subcutaneous fat (Figure 2). All cases of epidermotropic CD8⁺ T-cell lymphoma express the CD8⁺ phenotype and most have a high Ki-67 proliferation index and are CD3, CD45RA, and/or T-cell intracellular antigen 1 positive.¹

Due to its aggressive nature, epidermotropic CD8⁺ T-cell lymphoma has a poor prognosis, with an average 5-year survival rate of 18% and median survival of 22.5 months.³ Treatment proves difficult as conventional therapies for CD4⁺ CTCL have proven ineffective for epidermotropic CD8⁺ T-cell lymphoma. Partial response has been seen with bexarotene alone and with total skin electron beam therapy combined with oral retinoids.¹

The Diagnosis: Epidermotropic CD8⁺ T-Cell Lymphoma

Epidermotropic CD8⁺ T-cell lymphoma is a rare aggressive form of cutaneous T-cell lymphoma (CTCL), accounting for less than 1% of all cases.¹ Since this subtype of CTCL was first described in 1999 by Berti et al,² approximately 45 cases have been reported in the literature.¹ It typically is found in elderly men and presents as disseminated or localized papules, patches, plaques, nodules, and tumors, often with central necrosis, ulceration, crusting, and hemorrhage (Figure 1).^1,3 These lesions rapidly progress and can affect any skin site, but acral accentuation and mucosal involvement are common.⁴ Due to the rapidly progressive nature of this disease, patients typically present with widespread plaque- and tumor-stage disease.³ Frequency of systemic spread is high, with metastasis to the central nervous system, lungs, and testes being most common. Lymph nodes typically are spared, helping to differentiate this form of CTCL from classic mycosis fungoides.

Diagnosis of epidermotropic CD8⁺ T-cell lymphoma is based on a combination of clinical, histopathologic, and immunohistochemical features. Histopathologic components include epidermotropism, particularly in the basal cell layer, in a pagetoid or linear pattern. A second feature is a dermal infiltrate consisting of a nodular or diffuse pattern of atypical lymphocytes that extend to the subcutaneous fat (Figure 2). All cases of epidermotropic CD8⁺ T-cell lymphoma express the CD8⁺ phenotype and most have a high Ki-67 proliferation index and are CD3, CD45RA, and/or T-cell intracellular antigen 1 positive.¹

Due to its aggressive nature, epidermotropic CD8⁺ T-cell lymphoma has a poor prognosis, with an average 5-year survival rate of 18% and median survival of 22.5 months.³ Treatment proves difficult as conventional therapies for CD4⁺ CTCL have proven ineffective for epidermotropic CD8⁺ T-cell lymphoma. Partial response has been seen with bexarotene alone and with total skin electron beam therapy combined with oral retinoids.¹

The Diagnosis: Dental Sinus Secondary to Osteonecrosis of the Jaw

Cone beam computed tomography revealed an area of lucency measuring 40×20 mm in the body of the right mandible (Figure). The patient subsequently underwent curettage of the wound with sequestrectomy of the involved area.

Osteonecrosis of the jaw is a form of avascular necrosis. It is an uncommon but potentially serious side effect of bisphosphonate use.¹ Bisphosphonates commonly are used as first-line therapy for osteoporosis, with proven efficacy to reduce fracture risk by exerting an antiresorptive effect on bones.² Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is defined by the American Association of Oral and Maxillofacial Surgeons as the presence of exposed necrotic bone in the maxillofacial region that has persisted for more than 8 weeks, with current or prior treatment with a bisphosphonate and absence of prior radiation therapy to the jaw.3 Bisphosphonate-related osteonecrosis of the jaw can be associated with infections, pathologic fractures, extraoral fistulae, or osteolysis extending to the inferior border.

Our patient had a dental sinus that resulted from the underlying BRONJ. The jawbones, unlike the long bones, are in a special environment in that both acute and chronic infections occur often within the bone, and surgical procedures as well as masticatory trauma expose the bone to a bacteria-laden environment.⁴ Infection around the root apex of a tooth results in a dental abscess and a sinus tract can develop from the abscess, draining either intraorally or extraorally.⁵ Facial sinus tracts can be either odontogenic or nonodontogenic, and sometimes the lesions of dental origin may be confused with dermatological lesions.

Bisphosphonates inhibit osteoclasts, which are responsible for bone resorption. Antiangiogenetic effects also have been reported in bisphosphonates, resulting in devitalized bone.⁶ The potent and prolonged inhibition of bone remodeling likely plays an important role in BRONJ. The more frequently occurring microdamage inflicted on the lower jawbone with mastication also may represent a contributory factor.⁷

Bisphosphonate-related osteonecrosis of the jaw more often is associated with the use of high-dose intravenous (IV) bisphosphonate in cancer-related hypercalcemia and less so with oral bisphosphonates, which are generally used to treat osteoporosis.³ In a Swedish study conducted from 2003 to 2010, 55 cases of BRONJ were documented in a population of 1.2 million individuals. The prevalence of BRONJ in patients on oral bisphosphonates and IV bisphosphonates was estimated to be 0.024% and 2.8%, respectively.⁸

Bisphosphonates are widely used worldwide as the main treatment of osteoporosis. The association between osteonecrosis of the jaw and oral bisphosphonates is contentious among the osteoporosis population, as most studies focus on IV bisphosphonate use in cancer patients.⁹ Bisphosphonate-related osteonecrosis of the jaw adversely affects the patient's quality of life, producing notable morbidity in afflicted patients. Thus, a complete dental assessment and treatment is recommended before the initiation of bisphosphonate treatment. The risk for developing BRONJ associated with oral bisphosphonates increases when the duration of therapy exceeds 3 years.³ It has been reported that antifracture efficacy would persist for 1 to 2 years following discontinuation of alendronate or risedronate that had been taken for 3 to 5 years, but patients with low bone mineral density at the femoral neck (T-score below -2.5) after 3 to 5 years of treatment of bisphosphonates are at the highest risk for vertebral fractures and therefore appear to benefit most from continuation of therapy.¹⁰ For dental procedures, the American Association of Oral and Maxillofacial Surgeons suggests that if systemic conditions persist, the clinician might consider discontinuation of oral bisphosphonates for a 3-month period before and after elective invasive dental surgery to lower the risk for BRONJ.³ When possible, invasive dentoalveolar procedures such as extractions should be avoided; conservative endodontic treatment is preferable.

Bisphosphonate-related osteonecrosis of the jaw is a devastating condition that is difficult to treat and manage, thus the focus should be on prevention through dental clearance prior to starting bisphosphonates. It also is crucial to have a high index of suspicion for BRONJ in patients presenting with orofacial lesions so that they can be treated expediently.

The Diagnosis: Dental Sinus Secondary to Osteonecrosis of the Jaw

Cone beam computed tomography revealed an area of lucency measuring 40×20 mm in the body of the right mandible (Figure). The patient subsequently underwent curettage of the wound with sequestrectomy of the involved area.

Osteonecrosis of the jaw is a form of avascular necrosis. It is an uncommon but potentially serious side effect of bisphosphonate use.¹ Bisphosphonates commonly are used as first-line therapy for osteoporosis, with proven efficacy to reduce fracture risk by exerting an antiresorptive effect on bones.² Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is defined by the American Association of Oral and Maxillofacial Surgeons as the presence of exposed necrotic bone in the maxillofacial region that has persisted for more than 8 weeks, with current or prior treatment with a bisphosphonate and absence of prior radiation therapy to the jaw.3 Bisphosphonate-related osteonecrosis of the jaw can be associated with infections, pathologic fractures, extraoral fistulae, or osteolysis extending to the inferior border.

Our patient had a dental sinus that resulted from the underlying BRONJ. The jawbones, unlike the long bones, are in a special environment in that both acute and chronic infections occur often within the bone, and surgical procedures as well as masticatory trauma expose the bone to a bacteria-laden environment.⁴ Infection around the root apex of a tooth results in a dental abscess and a sinus tract can develop from the abscess, draining either intraorally or extraorally.⁵ Facial sinus tracts can be either odontogenic or nonodontogenic, and sometimes the lesions of dental origin may be confused with dermatological lesions.

Bisphosphonates inhibit osteoclasts, which are responsible for bone resorption. Antiangiogenetic effects also have been reported in bisphosphonates, resulting in devitalized bone.⁶ The potent and prolonged inhibition of bone remodeling likely plays an important role in BRONJ. The more frequently occurring microdamage inflicted on the lower jawbone with mastication also may represent a contributory factor.⁷

Bisphosphonate-related osteonecrosis of the jaw more often is associated with the use of high-dose intravenous (IV) bisphosphonate in cancer-related hypercalcemia and less so with oral bisphosphonates, which are generally used to treat osteoporosis.³ In a Swedish study conducted from 2003 to 2010, 55 cases of BRONJ were documented in a population of 1.2 million individuals. The prevalence of BRONJ in patients on oral bisphosphonates and IV bisphosphonates was estimated to be 0.024% and 2.8%, respectively.⁸

Bisphosphonates are widely used worldwide as the main treatment of osteoporosis. The association between osteonecrosis of the jaw and oral bisphosphonates is contentious among the osteoporosis population, as most studies focus on IV bisphosphonate use in cancer patients.⁹ Bisphosphonate-related osteonecrosis of the jaw adversely affects the patient's quality of life, producing notable morbidity in afflicted patients. Thus, a complete dental assessment and treatment is recommended before the initiation of bisphosphonate treatment. The risk for developing BRONJ associated with oral bisphosphonates increases when the duration of therapy exceeds 3 years.³ It has been reported that antifracture efficacy would persist for 1 to 2 years following discontinuation of alendronate or risedronate that had been taken for 3 to 5 years, but patients with low bone mineral density at the femoral neck (T-score below -2.5) after 3 to 5 years of treatment of bisphosphonates are at the highest risk for vertebral fractures and therefore appear to benefit most from continuation of therapy.¹⁰ For dental procedures, the American Association of Oral and Maxillofacial Surgeons suggests that if systemic conditions persist, the clinician might consider discontinuation of oral bisphosphonates for a 3-month period before and after elective invasive dental surgery to lower the risk for BRONJ.³ When possible, invasive dentoalveolar procedures such as extractions should be avoided; conservative endodontic treatment is preferable.

Bisphosphonate-related osteonecrosis of the jaw is a devastating condition that is difficult to treat and manage, thus the focus should be on prevention through dental clearance prior to starting bisphosphonates. It also is crucial to have a high index of suspicion for BRONJ in patients presenting with orofacial lesions so that they can be treated expediently.

The Diagnosis: Dental Sinus Secondary to Osteonecrosis of the Jaw

Cone beam computed tomography revealed an area of lucency measuring 40×20 mm in the body of the right mandible (Figure). The patient subsequently underwent curettage of the wound with sequestrectomy of the involved area.

Osteonecrosis of the jaw is a form of avascular necrosis. It is an uncommon but potentially serious side effect of bisphosphonate use.¹ Bisphosphonates commonly are used as first-line therapy for osteoporosis, with proven efficacy to reduce fracture risk by exerting an antiresorptive effect on bones.² Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is defined by the American Association of Oral and Maxillofacial Surgeons as the presence of exposed necrotic bone in the maxillofacial region that has persisted for more than 8 weeks, with current or prior treatment with a bisphosphonate and absence of prior radiation therapy to the jaw.3 Bisphosphonate-related osteonecrosis of the jaw can be associated with infections, pathologic fractures, extraoral fistulae, or osteolysis extending to the inferior border.

Our patient had a dental sinus that resulted from the underlying BRONJ. The jawbones, unlike the long bones, are in a special environment in that both acute and chronic infections occur often within the bone, and surgical procedures as well as masticatory trauma expose the bone to a bacteria-laden environment.⁴ Infection around the root apex of a tooth results in a dental abscess and a sinus tract can develop from the abscess, draining either intraorally or extraorally.⁵ Facial sinus tracts can be either odontogenic or nonodontogenic, and sometimes the lesions of dental origin may be confused with dermatological lesions.

Bisphosphonates inhibit osteoclasts, which are responsible for bone resorption. Antiangiogenetic effects also have been reported in bisphosphonates, resulting in devitalized bone.⁶ The potent and prolonged inhibition of bone remodeling likely plays an important role in BRONJ. The more frequently occurring microdamage inflicted on the lower jawbone with mastication also may represent a contributory factor.⁷

Bisphosphonate-related osteonecrosis of the jaw more often is associated with the use of high-dose intravenous (IV) bisphosphonate in cancer-related hypercalcemia and less so with oral bisphosphonates, which are generally used to treat osteoporosis.³ In a Swedish study conducted from 2003 to 2010, 55 cases of BRONJ were documented in a population of 1.2 million individuals. The prevalence of BRONJ in patients on oral bisphosphonates and IV bisphosphonates was estimated to be 0.024% and 2.8%, respectively.⁸

Bisphosphonates are widely used worldwide as the main treatment of osteoporosis. The association between osteonecrosis of the jaw and oral bisphosphonates is contentious among the osteoporosis population, as most studies focus on IV bisphosphonate use in cancer patients.⁹ Bisphosphonate-related osteonecrosis of the jaw adversely affects the patient's quality of life, producing notable morbidity in afflicted patients. Thus, a complete dental assessment and treatment is recommended before the initiation of bisphosphonate treatment. The risk for developing BRONJ associated with oral bisphosphonates increases when the duration of therapy exceeds 3 years.³ It has been reported that antifracture efficacy would persist for 1 to 2 years following discontinuation of alendronate or risedronate that had been taken for 3 to 5 years, but patients with low bone mineral density at the femoral neck (T-score below -2.5) after 3 to 5 years of treatment of bisphosphonates are at the highest risk for vertebral fractures and therefore appear to benefit most from continuation of therapy.¹⁰ For dental procedures, the American Association of Oral and Maxillofacial Surgeons suggests that if systemic conditions persist, the clinician might consider discontinuation of oral bisphosphonates for a 3-month period before and after elective invasive dental surgery to lower the risk for BRONJ.³ When possible, invasive dentoalveolar procedures such as extractions should be avoided; conservative endodontic treatment is preferable.

Bisphosphonate-related osteonecrosis of the jaw is a devastating condition that is difficult to treat and manage, thus the focus should be on prevention through dental clearance prior to starting bisphosphonates. It also is crucial to have a high index of suspicion for BRONJ in patients presenting with orofacial lesions so that they can be treated expediently.

The Diagnosis: Sister Mary Joseph Nodule

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

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

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

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

The Diagnosis: Sister Mary Joseph Nodule

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

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

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

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

The Diagnosis: Sister Mary Joseph Nodule

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

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

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

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

The Diagnosis: Lichen Striatus

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

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

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

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

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

The Diagnosis: Lichen Striatus

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

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

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

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

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

The Diagnosis: Lichen Striatus

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

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

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

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

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

The Diagnosis: Lipoid Proteinosis

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

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

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

The Diagnosis: Lipoid Proteinosis

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

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

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

The Diagnosis: Lipoid Proteinosis

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

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

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

The Diagnosis: Erythema Ab Igne

Given the patient's reticulated hyperpigmented lesions in the setting of recent space heater use with heater closer to the more affected leg, erythema ab igne was diagnosed. Patient education was provided and moving the heater away from the lower extremities was advised.

Erythema ab igne first was described by German dermatologist Abraham Buschke as hitze melanose, meaning melanosis induced by heat. The classic skin findings were first observed on the lower legs of patients who worked in front of open fires or coal stoves.¹ Over the years, new causes of erythema ab igne secondary to prolonged thermal radiation exposure have been reported.¹ In the elderly, hospitalized, and chronic pain patients, erythema ab igne has been observed in areas treated with heating pads and blankets.² Other triggers such as frequent hot bathing, furniture, steam radiators, space heaters, and laptops also have been reported.^3-6 Laptop-induced erythema ab igne is a diagnosis that has been reported in the last decade and its incidence likely will increase in the future.⁶

The clinical manifestations of erythema ab igne correlate with the frequency and duration of heat exposure. Acutely, a mild and transient erythema develops in the affected area. With chronic heat exposure, these areas subsequently develop a permanent reticulated hyperpigmented pattern and may eventually become atrophic.^2,6 All body surfaces are at risk, but erythema ab igne classically involves the legs, lower back, and/or abdomen. Lesions typically are asymptomatic; however, burning and pruritus can be present.^2,6 Bullous erythema ab igne, though rare, has been reported,⁷ suggesting a potential transition from erythema ab igne to burns.⁶

Biopsy is not recommended for diagnosis; however, the histopathologic changes of erythema ab igne include hyperkeratosis, interface dermatitis, epidermal atrophy with apoptotic keratinocytes, and melanin incontinence. Although this condition typically is benign, histologic findings could resemble actinic keratosis, suggesting that chronic changes induced by infrared thermal radiation may lead to squamous cell carcinoma or rarely Merkel cell carcinoma. The latency for developing carcinoma appears to extend 30 years, with a 30% tendency for recurrence or metastasis. Given the possibility of an increase in erythema ab igne in the pediatric population in the upcoming years, as displayed by our patient, and increasing laptop and electronic use in children and adolescents, it is important to be aware of this skin condition and the potential complications of it going undiagnosed.^2,6

No specific therapy for erythema ab igne exists. Treatment is centered on eliminating exposure to the heat source. With appropriate removal, the reticulated hyperpigmented lesions will resolve, sometimes taking several months.

Differential diagnosis includes livedo reticularis, livedoid vasculopathy, and cutis marmorata. The reticulated purpuric lesions of livedo reticularis involving the extremities often mimic erythema ab igne's cutaneous morphology; however, livedo reticularis frequently is associated with conditions such as drug reactions, infections, thrombosis, and vasculitides,² as opposed to erythema ab igne, which frequently is associated with conditions causing pain or decreased body temperature, thus necessitating use of heating devices, as seen in our patient. Livedoid vasculopathy is characterized by purpuric macules involving the lower legs and feet that progress to recurrent leg ulcers. Our patient's asymptomatic lesions and absence of ulcers excluded this diagnosis.⁸ Lastly, cutis marmorata, a congenital condition, is characterized by blue-violet vascular networks that often display ulceration and atrophy of the involved skin as well as hypertrophy or atrophy of the involved limb⁹; these clinical findings were not present in our patient and this diagnosis would not explain the relationship between the cutaneous lesions and heat exposure. 

The Diagnosis: Erythema Ab Igne

Given the patient's reticulated hyperpigmented lesions in the setting of recent space heater use with heater closer to the more affected leg, erythema ab igne was diagnosed. Patient education was provided and moving the heater away from the lower extremities was advised.

Erythema ab igne first was described by German dermatologist Abraham Buschke as hitze melanose, meaning melanosis induced by heat. The classic skin findings were first observed on the lower legs of patients who worked in front of open fires or coal stoves.¹ Over the years, new causes of erythema ab igne secondary to prolonged thermal radiation exposure have been reported.¹ In the elderly, hospitalized, and chronic pain patients, erythema ab igne has been observed in areas treated with heating pads and blankets.² Other triggers such as frequent hot bathing, furniture, steam radiators, space heaters, and laptops also have been reported.^3-6 Laptop-induced erythema ab igne is a diagnosis that has been reported in the last decade and its incidence likely will increase in the future.⁶

The clinical manifestations of erythema ab igne correlate with the frequency and duration of heat exposure. Acutely, a mild and transient erythema develops in the affected area. With chronic heat exposure, these areas subsequently develop a permanent reticulated hyperpigmented pattern and may eventually become atrophic.^2,6 All body surfaces are at risk, but erythema ab igne classically involves the legs, lower back, and/or abdomen. Lesions typically are asymptomatic; however, burning and pruritus can be present.^2,6 Bullous erythema ab igne, though rare, has been reported,⁷ suggesting a potential transition from erythema ab igne to burns.⁶

Biopsy is not recommended for diagnosis; however, the histopathologic changes of erythema ab igne include hyperkeratosis, interface dermatitis, epidermal atrophy with apoptotic keratinocytes, and melanin incontinence. Although this condition typically is benign, histologic findings could resemble actinic keratosis, suggesting that chronic changes induced by infrared thermal radiation may lead to squamous cell carcinoma or rarely Merkel cell carcinoma. The latency for developing carcinoma appears to extend 30 years, with a 30% tendency for recurrence or metastasis. Given the possibility of an increase in erythema ab igne in the pediatric population in the upcoming years, as displayed by our patient, and increasing laptop and electronic use in children and adolescents, it is important to be aware of this skin condition and the potential complications of it going undiagnosed.^2,6

No specific therapy for erythema ab igne exists. Treatment is centered on eliminating exposure to the heat source. With appropriate removal, the reticulated hyperpigmented lesions will resolve, sometimes taking several months.

Differential diagnosis includes livedo reticularis, livedoid vasculopathy, and cutis marmorata. The reticulated purpuric lesions of livedo reticularis involving the extremities often mimic erythema ab igne's cutaneous morphology; however, livedo reticularis frequently is associated with conditions such as drug reactions, infections, thrombosis, and vasculitides,² as opposed to erythema ab igne, which frequently is associated with conditions causing pain or decreased body temperature, thus necessitating use of heating devices, as seen in our patient. Livedoid vasculopathy is characterized by purpuric macules involving the lower legs and feet that progress to recurrent leg ulcers. Our patient's asymptomatic lesions and absence of ulcers excluded this diagnosis.⁸ Lastly, cutis marmorata, a congenital condition, is characterized by blue-violet vascular networks that often display ulceration and atrophy of the involved skin as well as hypertrophy or atrophy of the involved limb⁹; these clinical findings were not present in our patient and this diagnosis would not explain the relationship between the cutaneous lesions and heat exposure. 

The Diagnosis: Erythema Ab Igne

Given the patient's reticulated hyperpigmented lesions in the setting of recent space heater use with heater closer to the more affected leg, erythema ab igne was diagnosed. Patient education was provided and moving the heater away from the lower extremities was advised.

Erythema ab igne first was described by German dermatologist Abraham Buschke as hitze melanose, meaning melanosis induced by heat. The classic skin findings were first observed on the lower legs of patients who worked in front of open fires or coal stoves.¹ Over the years, new causes of erythema ab igne secondary to prolonged thermal radiation exposure have been reported.¹ In the elderly, hospitalized, and chronic pain patients, erythema ab igne has been observed in areas treated with heating pads and blankets.² Other triggers such as frequent hot bathing, furniture, steam radiators, space heaters, and laptops also have been reported.^3-6 Laptop-induced erythema ab igne is a diagnosis that has been reported in the last decade and its incidence likely will increase in the future.⁶

The clinical manifestations of erythema ab igne correlate with the frequency and duration of heat exposure. Acutely, a mild and transient erythema develops in the affected area. With chronic heat exposure, these areas subsequently develop a permanent reticulated hyperpigmented pattern and may eventually become atrophic.^2,6 All body surfaces are at risk, but erythema ab igne classically involves the legs, lower back, and/or abdomen. Lesions typically are asymptomatic; however, burning and pruritus can be present.^2,6 Bullous erythema ab igne, though rare, has been reported,⁷ suggesting a potential transition from erythema ab igne to burns.⁶

Biopsy is not recommended for diagnosis; however, the histopathologic changes of erythema ab igne include hyperkeratosis, interface dermatitis, epidermal atrophy with apoptotic keratinocytes, and melanin incontinence. Although this condition typically is benign, histologic findings could resemble actinic keratosis, suggesting that chronic changes induced by infrared thermal radiation may lead to squamous cell carcinoma or rarely Merkel cell carcinoma. The latency for developing carcinoma appears to extend 30 years, with a 30% tendency for recurrence or metastasis. Given the possibility of an increase in erythema ab igne in the pediatric population in the upcoming years, as displayed by our patient, and increasing laptop and electronic use in children and adolescents, it is important to be aware of this skin condition and the potential complications of it going undiagnosed.^2,6

No specific therapy for erythema ab igne exists. Treatment is centered on eliminating exposure to the heat source. With appropriate removal, the reticulated hyperpigmented lesions will resolve, sometimes taking several months.

Differential diagnosis includes livedo reticularis, livedoid vasculopathy, and cutis marmorata. The reticulated purpuric lesions of livedo reticularis involving the extremities often mimic erythema ab igne's cutaneous morphology; however, livedo reticularis frequently is associated with conditions such as drug reactions, infections, thrombosis, and vasculitides,² as opposed to erythema ab igne, which frequently is associated with conditions causing pain or decreased body temperature, thus necessitating use of heating devices, as seen in our patient. Livedoid vasculopathy is characterized by purpuric macules involving the lower legs and feet that progress to recurrent leg ulcers. Our patient's asymptomatic lesions and absence of ulcers excluded this diagnosis.⁸ Lastly, cutis marmorata, a congenital condition, is characterized by blue-violet vascular networks that often display ulceration and atrophy of the involved skin as well as hypertrophy or atrophy of the involved limb⁹; these clinical findings were not present in our patient and this diagnosis would not explain the relationship between the cutaneous lesions and heat exposure. 

The Diagnosis: Blue Toe Syndrome

The clinical manifestation suggested blue toe syndrome. A variety of causes for blue toe syndrome are known such as embolism, thrombosis, vasoconstrictive disorders, infectious and noninfectious inflammation, extensive venous thrombosis, and abnormal circulating blood.¹ Among them, only emboli from atherosclerotic plaques give rise to typical cholesterol clefts on skin biopsy (Figure 1). Such atheroemboli often are an iatrogenic complication, especially those caused by invasive percutaneous procedures or damage to the arterial walls from vascular surgery. However, spontaneous plaque hemorrhage or shearing forces of the circulating blood can disrupt atheromatous plaques and cause embolization of the cholesterol crystals, which was likely to be the case in our patient because no preceding trigger events were noted.

Other clinical features also are seen in atheroembolism. Approximately half of patients with atheroembolism develop clinical kidney disease.² Almost all iatrogenic cases have acute or subacute reduction in glomerular filtration rate of at least to 50% level, whereas the spontaneous cases present as stable chronic renal failure.³ Approximately 20% of patients with atheroembolism also have involvement of digestive organs.^4,5 Abdominal pain, diarrhea, and gastrointestinal blood loss are common features; bowel infarction and perforation occasionally occur.⁵ Pancreatitis is another common complication, and serum amylase levels are raised in approximately 50% of patients.6 Atheroemboli may reach the eyes and brain. They occasionally can cause loss of vision,⁷ as well as transient ischemic attacks, strokes, and gradual deterioration in cerebral function.³ Blood eosinophilia, which occurs in approximately 60% of patients, is an important finding.^3,8

Although there is no specific therapy for atheroembolism, the use of antiplatelet agents is considered reasonable because they are beneficial in preventing myocardial infarction in patients with atherosclerosis.⁹ In our case, the livedo reticularis cleared, as did the coldness on the affected toes after 2 weeks of sarpogrelate hydrochloride administration; however, development of necrotic change was noted (Figure 2). Necrotic change on the hallux disappeared after 2 weeks.

The Diagnosis: Blue Toe Syndrome

The clinical manifestation suggested blue toe syndrome. A variety of causes for blue toe syndrome are known such as embolism, thrombosis, vasoconstrictive disorders, infectious and noninfectious inflammation, extensive venous thrombosis, and abnormal circulating blood.¹ Among them, only emboli from atherosclerotic plaques give rise to typical cholesterol clefts on skin biopsy (Figure 1). Such atheroemboli often are an iatrogenic complication, especially those caused by invasive percutaneous procedures or damage to the arterial walls from vascular surgery. However, spontaneous plaque hemorrhage or shearing forces of the circulating blood can disrupt atheromatous plaques and cause embolization of the cholesterol crystals, which was likely to be the case in our patient because no preceding trigger events were noted.

Other clinical features also are seen in atheroembolism. Approximately half of patients with atheroembolism develop clinical kidney disease.² Almost all iatrogenic cases have acute or subacute reduction in glomerular filtration rate of at least to 50% level, whereas the spontaneous cases present as stable chronic renal failure.³ Approximately 20% of patients with atheroembolism also have involvement of digestive organs.^4,5 Abdominal pain, diarrhea, and gastrointestinal blood loss are common features; bowel infarction and perforation occasionally occur.⁵ Pancreatitis is another common complication, and serum amylase levels are raised in approximately 50% of patients.6 Atheroemboli may reach the eyes and brain. They occasionally can cause loss of vision,⁷ as well as transient ischemic attacks, strokes, and gradual deterioration in cerebral function.³ Blood eosinophilia, which occurs in approximately 60% of patients, is an important finding.^3,8

Although there is no specific therapy for atheroembolism, the use of antiplatelet agents is considered reasonable because they are beneficial in preventing myocardial infarction in patients with atherosclerosis.⁹ In our case, the livedo reticularis cleared, as did the coldness on the affected toes after 2 weeks of sarpogrelate hydrochloride administration; however, development of necrotic change was noted (Figure 2). Necrotic change on the hallux disappeared after 2 weeks.

The Diagnosis: Blue Toe Syndrome

The clinical manifestation suggested blue toe syndrome. A variety of causes for blue toe syndrome are known such as embolism, thrombosis, vasoconstrictive disorders, infectious and noninfectious inflammation, extensive venous thrombosis, and abnormal circulating blood.¹ Among them, only emboli from atherosclerotic plaques give rise to typical cholesterol clefts on skin biopsy (Figure 1). Such atheroemboli often are an iatrogenic complication, especially those caused by invasive percutaneous procedures or damage to the arterial walls from vascular surgery. However, spontaneous plaque hemorrhage or shearing forces of the circulating blood can disrupt atheromatous plaques and cause embolization of the cholesterol crystals, which was likely to be the case in our patient because no preceding trigger events were noted.

Other clinical features also are seen in atheroembolism. Approximately half of patients with atheroembolism develop clinical kidney disease.² Almost all iatrogenic cases have acute or subacute reduction in glomerular filtration rate of at least to 50% level, whereas the spontaneous cases present as stable chronic renal failure.³ Approximately 20% of patients with atheroembolism also have involvement of digestive organs.^4,5 Abdominal pain, diarrhea, and gastrointestinal blood loss are common features; bowel infarction and perforation occasionally occur.⁵ Pancreatitis is another common complication, and serum amylase levels are raised in approximately 50% of patients.6 Atheroemboli may reach the eyes and brain. They occasionally can cause loss of vision,⁷ as well as transient ischemic attacks, strokes, and gradual deterioration in cerebral function.³ Blood eosinophilia, which occurs in approximately 60% of patients, is an important finding.^3,8

Although there is no specific therapy for atheroembolism, the use of antiplatelet agents is considered reasonable because they are beneficial in preventing myocardial infarction in patients with atherosclerosis.⁹ In our case, the livedo reticularis cleared, as did the coldness on the affected toes after 2 weeks of sarpogrelate hydrochloride administration; however, development of necrotic change was noted (Figure 2). Necrotic change on the hallux disappeared after 2 weeks.

The Diagnosis: Secondary Syphilis

Syphilis, known as the great mimicker, has a wide-ranging clinical and histologic presentation. There can be overlapping features with many of the entities included in the differential diagnoses. As our patient exemplifies, clinicians and pathologists must have a high index of suspicion, and any concerning features should lead to a more in-depth patient history, spirochete stains, and serologic testing.

Our patient was seen by several dermatologists over the course of 2 years and therapy with topical steroids failed. He was eager to pursue more aggressive therapy with methotrexate, and a punch biopsy was performed to confirm the diagnosis of psoriasis prior to initiating treatment. Hematoxylin and eosin staining results on low power can be seen in Figure 1A. Medium-power view demonstrated vacuolar interface dermatitis (Figure 1B) with psoriasiform epidermal hyperplasia with slender elongation of rete ridges; neutrophils in the stratum corneum; endothelial cell swelling (Figure 1C); and mixed infiltrate with high plasma cells (Figure 1D), lymphocytes, and histiocytes. Although the biopsy results were psoriasiform, there was high suspicion for syphilis in this case. Additional staining for spirochetes was performed with syphilis immunohistochemical stain¹ (Figure 2), which revealed spirochetes present on the patient's biopsy, confirming the diagnosis of syphilis. Warthin-Starry stain also can be performed to confirm the diagnosis.

Based on histologic features, the differential diagnosis includes psoriasis vulgaris, eczema, lichen planus, or lichenoid drug eruption. Psoriasis vulgaris displays regular psoriasiform epidermal hyperplasia with hypergranulosis and confluent parakeratosis. The elongated rete pegs are broad rather than slender.² Neutrophils are present in the stratum corneum. In contrast, eczematous dermatitis is characterized by epidermal hyperplasia, spongiosis, parakeratosis, and eosinophils. Lichen planus classically displays a brisk bandlike lymphocytic infiltrate that closely abuts or obscures the dermoepidermal junction. Parakeratosis, neutrophils, and eosinophils should be absent. The rete pegs taper to a point, similar to a sawtooth, while they are long and slender with syphilis, similar to an ice pick. Although lichenoid drug eruption presents with interface dermatitis, parakeratosis, and eosinophils, the epidermis is hyperplastic without the slender elongation of rete pegs seen in syphilis.

Further workup with serologic testing demonstrated that the patient had a syphilis IgG titer of greater than 8.0 (reactive, >6.0), indicating the patient had been infected.³ Reactive syphilis IgG, a specific treponemal test, should be followed with a nontreponemal assay of either rapid plasma reagin (RPR) or VDRL test to confirm disease activity, according to recommendations from the Centers for Disease Control and Prevention,4 which represents a change to the traditional algorithm that called for screening with a nontreponemal test and confirming with a specific treponemal test. The patient had a positive RPR and quantitative RPR titer was found as 1:2048, indicating that syphilis was active or recently treated. Testing for human immunodeficiency virus (HIV) revealed a quantitative RNA polymerase chain reaction of 145,000 copies/mL and a CD4 count of 18 cells/µL (reference range, 533-1674 cells/µL).

The patient initially was treated for latent syphilis with 3 doses of intramuscular penicillin G benzathine 2.4 million U once weekly for 3 weeks. Due to his high RPR titers and low CD4 count, a lumbar puncture was later pursued, which revealed positive results from a cerebrospinal fluid (CSF)-VDRL test, confirming a diagnosis of neurosyphilis. Although a positive CSF-VDRL test is specific for the diagnosis of neurosyphilis, the sensitivity of the CSF-VDRL test against clinical diagnosis is only 30% to 70%.⁵ Intravenous aqueous penicillin G 4 million U every 4 hours was started for 14 days for neurosyphilis. One month following the completion of the intravenous penicillin, the rash completely resolved. The patient was in a 10-year monogamous relationship with a man and did not use condoms. Typically, signs and symptoms of secondary syphilis begin 4 to 10 weeks after the appearance of a chancre. However, the classic chancre of primary syphilis among men who have sex with men may go unnoticed in those who may not be able to see anal lesions.⁶ Also, infection with syphilis increases the likelihood of acquiring and transmitting HIV. All patients diagnosed with syphilis should have additional testing for HIV and other sexually transmitted diseases. 

For patients with a history of thick scaly plaques on the wrists, knees, and feet resistant to topical steroid therapy, dermatologists should maintain a high index of clinical suspicion for syphilis. 

The Diagnosis: Secondary Syphilis

Syphilis, known as the great mimicker, has a wide-ranging clinical and histologic presentation. There can be overlapping features with many of the entities included in the differential diagnoses. As our patient exemplifies, clinicians and pathologists must have a high index of suspicion, and any concerning features should lead to a more in-depth patient history, spirochete stains, and serologic testing.

Our patient was seen by several dermatologists over the course of 2 years and therapy with topical steroids failed. He was eager to pursue more aggressive therapy with methotrexate, and a punch biopsy was performed to confirm the diagnosis of psoriasis prior to initiating treatment. Hematoxylin and eosin staining results on low power can be seen in Figure 1A. Medium-power view demonstrated vacuolar interface dermatitis (Figure 1B) with psoriasiform epidermal hyperplasia with slender elongation of rete ridges; neutrophils in the stratum corneum; endothelial cell swelling (Figure 1C); and mixed infiltrate with high plasma cells (Figure 1D), lymphocytes, and histiocytes. Although the biopsy results were psoriasiform, there was high suspicion for syphilis in this case. Additional staining for spirochetes was performed with syphilis immunohistochemical stain¹ (Figure 2), which revealed spirochetes present on the patient's biopsy, confirming the diagnosis of syphilis. Warthin-Starry stain also can be performed to confirm the diagnosis.

Based on histologic features, the differential diagnosis includes psoriasis vulgaris, eczema, lichen planus, or lichenoid drug eruption. Psoriasis vulgaris displays regular psoriasiform epidermal hyperplasia with hypergranulosis and confluent parakeratosis. The elongated rete pegs are broad rather than slender.² Neutrophils are present in the stratum corneum. In contrast, eczematous dermatitis is characterized by epidermal hyperplasia, spongiosis, parakeratosis, and eosinophils. Lichen planus classically displays a brisk bandlike lymphocytic infiltrate that closely abuts or obscures the dermoepidermal junction. Parakeratosis, neutrophils, and eosinophils should be absent. The rete pegs taper to a point, similar to a sawtooth, while they are long and slender with syphilis, similar to an ice pick. Although lichenoid drug eruption presents with interface dermatitis, parakeratosis, and eosinophils, the epidermis is hyperplastic without the slender elongation of rete pegs seen in syphilis.

Further workup with serologic testing demonstrated that the patient had a syphilis IgG titer of greater than 8.0 (reactive, >6.0), indicating the patient had been infected.³ Reactive syphilis IgG, a specific treponemal test, should be followed with a nontreponemal assay of either rapid plasma reagin (RPR) or VDRL test to confirm disease activity, according to recommendations from the Centers for Disease Control and Prevention,4 which represents a change to the traditional algorithm that called for screening with a nontreponemal test and confirming with a specific treponemal test. The patient had a positive RPR and quantitative RPR titer was found as 1:2048, indicating that syphilis was active or recently treated. Testing for human immunodeficiency virus (HIV) revealed a quantitative RNA polymerase chain reaction of 145,000 copies/mL and a CD4 count of 18 cells/µL (reference range, 533-1674 cells/µL).

The patient initially was treated for latent syphilis with 3 doses of intramuscular penicillin G benzathine 2.4 million U once weekly for 3 weeks. Due to his high RPR titers and low CD4 count, a lumbar puncture was later pursued, which revealed positive results from a cerebrospinal fluid (CSF)-VDRL test, confirming a diagnosis of neurosyphilis. Although a positive CSF-VDRL test is specific for the diagnosis of neurosyphilis, the sensitivity of the CSF-VDRL test against clinical diagnosis is only 30% to 70%.⁵ Intravenous aqueous penicillin G 4 million U every 4 hours was started for 14 days for neurosyphilis. One month following the completion of the intravenous penicillin, the rash completely resolved. The patient was in a 10-year monogamous relationship with a man and did not use condoms. Typically, signs and symptoms of secondary syphilis begin 4 to 10 weeks after the appearance of a chancre. However, the classic chancre of primary syphilis among men who have sex with men may go unnoticed in those who may not be able to see anal lesions.⁶ Also, infection with syphilis increases the likelihood of acquiring and transmitting HIV. All patients diagnosed with syphilis should have additional testing for HIV and other sexually transmitted diseases. 

For patients with a history of thick scaly plaques on the wrists, knees, and feet resistant to topical steroid therapy, dermatologists should maintain a high index of clinical suspicion for syphilis. 

The Diagnosis: Secondary Syphilis

Syphilis, known as the great mimicker, has a wide-ranging clinical and histologic presentation. There can be overlapping features with many of the entities included in the differential diagnoses. As our patient exemplifies, clinicians and pathologists must have a high index of suspicion, and any concerning features should lead to a more in-depth patient history, spirochete stains, and serologic testing.

Our patient was seen by several dermatologists over the course of 2 years and therapy with topical steroids failed. He was eager to pursue more aggressive therapy with methotrexate, and a punch biopsy was performed to confirm the diagnosis of psoriasis prior to initiating treatment. Hematoxylin and eosin staining results on low power can be seen in Figure 1A. Medium-power view demonstrated vacuolar interface dermatitis (Figure 1B) with psoriasiform epidermal hyperplasia with slender elongation of rete ridges; neutrophils in the stratum corneum; endothelial cell swelling (Figure 1C); and mixed infiltrate with high plasma cells (Figure 1D), lymphocytes, and histiocytes. Although the biopsy results were psoriasiform, there was high suspicion for syphilis in this case. Additional staining for spirochetes was performed with syphilis immunohistochemical stain¹ (Figure 2), which revealed spirochetes present on the patient's biopsy, confirming the diagnosis of syphilis. Warthin-Starry stain also can be performed to confirm the diagnosis.

Based on histologic features, the differential diagnosis includes psoriasis vulgaris, eczema, lichen planus, or lichenoid drug eruption. Psoriasis vulgaris displays regular psoriasiform epidermal hyperplasia with hypergranulosis and confluent parakeratosis. The elongated rete pegs are broad rather than slender.² Neutrophils are present in the stratum corneum. In contrast, eczematous dermatitis is characterized by epidermal hyperplasia, spongiosis, parakeratosis, and eosinophils. Lichen planus classically displays a brisk bandlike lymphocytic infiltrate that closely abuts or obscures the dermoepidermal junction. Parakeratosis, neutrophils, and eosinophils should be absent. The rete pegs taper to a point, similar to a sawtooth, while they are long and slender with syphilis, similar to an ice pick. Although lichenoid drug eruption presents with interface dermatitis, parakeratosis, and eosinophils, the epidermis is hyperplastic without the slender elongation of rete pegs seen in syphilis.

Further workup with serologic testing demonstrated that the patient had a syphilis IgG titer of greater than 8.0 (reactive, >6.0), indicating the patient had been infected.³ Reactive syphilis IgG, a specific treponemal test, should be followed with a nontreponemal assay of either rapid plasma reagin (RPR) or VDRL test to confirm disease activity, according to recommendations from the Centers for Disease Control and Prevention,4 which represents a change to the traditional algorithm that called for screening with a nontreponemal test and confirming with a specific treponemal test. The patient had a positive RPR and quantitative RPR titer was found as 1:2048, indicating that syphilis was active or recently treated. Testing for human immunodeficiency virus (HIV) revealed a quantitative RNA polymerase chain reaction of 145,000 copies/mL and a CD4 count of 18 cells/µL (reference range, 533-1674 cells/µL).

The patient initially was treated for latent syphilis with 3 doses of intramuscular penicillin G benzathine 2.4 million U once weekly for 3 weeks. Due to his high RPR titers and low CD4 count, a lumbar puncture was later pursued, which revealed positive results from a cerebrospinal fluid (CSF)-VDRL test, confirming a diagnosis of neurosyphilis. Although a positive CSF-VDRL test is specific for the diagnosis of neurosyphilis, the sensitivity of the CSF-VDRL test against clinical diagnosis is only 30% to 70%.⁵ Intravenous aqueous penicillin G 4 million U every 4 hours was started for 14 days for neurosyphilis. One month following the completion of the intravenous penicillin, the rash completely resolved. The patient was in a 10-year monogamous relationship with a man and did not use condoms. Typically, signs and symptoms of secondary syphilis begin 4 to 10 weeks after the appearance of a chancre. However, the classic chancre of primary syphilis among men who have sex with men may go unnoticed in those who may not be able to see anal lesions.⁶ Also, infection with syphilis increases the likelihood of acquiring and transmitting HIV. All patients diagnosed with syphilis should have additional testing for HIV and other sexually transmitted diseases. 

For patients with a history of thick scaly plaques on the wrists, knees, and feet resistant to topical steroid therapy, dermatologists should maintain a high index of clinical suspicion for syphilis. 

The Diagnosis: Livedoid Vasculopathy

Livedoid vasculopathy (LV) is a rare cutaneous disorder that most commonly affects the lower legs. It has an estimated incidence of 1 case per 100,000 per year and predominantly affects women.¹ The disease pathogenesis is not fully understood but is thought to involve thrombosis and occlusion of dermal vessels resulting in tissue hypoxia.² Both inherited and acquired thrombophilic conditions frequently are seen in patients with LV.^3,4 Livedoid vasculopathy also has been described as idiopathic⁵ and is associated with immune complex deposition.⁶ However, the number of cases of idiopathic LV may be overestimated; as technological advancements to detect coagulation abnormalities improve, it is hypothesized that this entity will be identified less often.^2,4

Livedoid vasculopathy has been described in the literature using the term PPURPLE (painful purpuric ulcers with reticular pattern of lower extremities).⁷ The triad of livedo racemosa, recurrent painful ulcerations, and residual healing with atrophie blanche characterizes the clinical manifestations of LV; however, all 3 characteristics do not need to appear simultaneously for a diagnosis to be made. The condition has a chronic course with spontaneous remissions and exacerbations. Episodic ulcerations occur, especially in the summertime, and heal slowly, leaving behind atrophic, porcelain white, stellate-shaped scars called atrophie blanche. Livedo racemosa also may be seen in Sneddon syndrome; however, these patients experience neurologic symptoms secondary to cerebrovascular occlusion. In contrast to livedo racemosa, acquired livedo reticularis represents a physiologic hypoperfusion pattern that occurs in response to cold exposure.⁸ A localized sharp pain, known as angina cutis, typically precedes the clinical symptom of painful ulcerations.⁹ Atrophie blanche once was thought to be specific to LV but has been seen in other diseases such as systemic lupus erythematosus and chronic venous insufficiency.²

The diagnosis of LV is based on identification of characteristic clinical features and skin biopsy. In almost all biopsy specimens, histopathology reveals fibrinoid occlusion of vessels in the superficial and mid dermis.⁴ Other findings may include epidermal necrosis and vessel wall hyalinization and infarction² (Figure). Because LV is commonly misdiagnosed as vasculitis, the absence of hallmark features of vasculitis such as neutrophilic infiltrate of blood vessel walls and fibrinoid necrosis suggest the diagnosis. Extensive laboratory evaluation for inherited and acquired coagulation abnormalities should be performed.

Treatment of LV is difficult, as there is currently no consensus on optimal therapy. The mainstay of therapy is to reduce pain, prevent infection, and reduce ulceration and development of atrophie blanche. Underlying causes should be identified and appropriately treated. Because the primary pathogenesis of LV is considered to be a hypercoagulable state, first-line treatment often includes therapies to enhance blood flow and prevent thrombosis such as smoking cessation, antiplatelet therapy, and pentoxifylline. Vasodilating agents, anti-inflammatory agents, anticoagulation, and fibrinolytic therapy also have been used with varying degrees of success.⁷

The Diagnosis: Livedoid Vasculopathy

Livedoid vasculopathy (LV) is a rare cutaneous disorder that most commonly affects the lower legs. It has an estimated incidence of 1 case per 100,000 per year and predominantly affects women.¹ The disease pathogenesis is not fully understood but is thought to involve thrombosis and occlusion of dermal vessels resulting in tissue hypoxia.² Both inherited and acquired thrombophilic conditions frequently are seen in patients with LV.^3,4 Livedoid vasculopathy also has been described as idiopathic⁵ and is associated with immune complex deposition.⁶ However, the number of cases of idiopathic LV may be overestimated; as technological advancements to detect coagulation abnormalities improve, it is hypothesized that this entity will be identified less often.^2,4

Livedoid vasculopathy has been described in the literature using the term PPURPLE (painful purpuric ulcers with reticular pattern of lower extremities).⁷ The triad of livedo racemosa, recurrent painful ulcerations, and residual healing with atrophie blanche characterizes the clinical manifestations of LV; however, all 3 characteristics do not need to appear simultaneously for a diagnosis to be made. The condition has a chronic course with spontaneous remissions and exacerbations. Episodic ulcerations occur, especially in the summertime, and heal slowly, leaving behind atrophic, porcelain white, stellate-shaped scars called atrophie blanche. Livedo racemosa also may be seen in Sneddon syndrome; however, these patients experience neurologic symptoms secondary to cerebrovascular occlusion. In contrast to livedo racemosa, acquired livedo reticularis represents a physiologic hypoperfusion pattern that occurs in response to cold exposure.⁸ A localized sharp pain, known as angina cutis, typically precedes the clinical symptom of painful ulcerations.⁹ Atrophie blanche once was thought to be specific to LV but has been seen in other diseases such as systemic lupus erythematosus and chronic venous insufficiency.²

The diagnosis of LV is based on identification of characteristic clinical features and skin biopsy. In almost all biopsy specimens, histopathology reveals fibrinoid occlusion of vessels in the superficial and mid dermis.⁴ Other findings may include epidermal necrosis and vessel wall hyalinization and infarction² (Figure). Because LV is commonly misdiagnosed as vasculitis, the absence of hallmark features of vasculitis such as neutrophilic infiltrate of blood vessel walls and fibrinoid necrosis suggest the diagnosis. Extensive laboratory evaluation for inherited and acquired coagulation abnormalities should be performed.

Treatment of LV is difficult, as there is currently no consensus on optimal therapy. The mainstay of therapy is to reduce pain, prevent infection, and reduce ulceration and development of atrophie blanche. Underlying causes should be identified and appropriately treated. Because the primary pathogenesis of LV is considered to be a hypercoagulable state, first-line treatment often includes therapies to enhance blood flow and prevent thrombosis such as smoking cessation, antiplatelet therapy, and pentoxifylline. Vasodilating agents, anti-inflammatory agents, anticoagulation, and fibrinolytic therapy also have been used with varying degrees of success.⁷

The Diagnosis: Livedoid Vasculopathy

Livedoid vasculopathy (LV) is a rare cutaneous disorder that most commonly affects the lower legs. It has an estimated incidence of 1 case per 100,000 per year and predominantly affects women.¹ The disease pathogenesis is not fully understood but is thought to involve thrombosis and occlusion of dermal vessels resulting in tissue hypoxia.² Both inherited and acquired thrombophilic conditions frequently are seen in patients with LV.^3,4 Livedoid vasculopathy also has been described as idiopathic⁵ and is associated with immune complex deposition.⁶ However, the number of cases of idiopathic LV may be overestimated; as technological advancements to detect coagulation abnormalities improve, it is hypothesized that this entity will be identified less often.^2,4

Livedoid vasculopathy has been described in the literature using the term PPURPLE (painful purpuric ulcers with reticular pattern of lower extremities).⁷ The triad of livedo racemosa, recurrent painful ulcerations, and residual healing with atrophie blanche characterizes the clinical manifestations of LV; however, all 3 characteristics do not need to appear simultaneously for a diagnosis to be made. The condition has a chronic course with spontaneous remissions and exacerbations. Episodic ulcerations occur, especially in the summertime, and heal slowly, leaving behind atrophic, porcelain white, stellate-shaped scars called atrophie blanche. Livedo racemosa also may be seen in Sneddon syndrome; however, these patients experience neurologic symptoms secondary to cerebrovascular occlusion. In contrast to livedo racemosa, acquired livedo reticularis represents a physiologic hypoperfusion pattern that occurs in response to cold exposure.⁸ A localized sharp pain, known as angina cutis, typically precedes the clinical symptom of painful ulcerations.⁹ Atrophie blanche once was thought to be specific to LV but has been seen in other diseases such as systemic lupus erythematosus and chronic venous insufficiency.²

The diagnosis of LV is based on identification of characteristic clinical features and skin biopsy. In almost all biopsy specimens, histopathology reveals fibrinoid occlusion of vessels in the superficial and mid dermis.⁴ Other findings may include epidermal necrosis and vessel wall hyalinization and infarction² (Figure). Because LV is commonly misdiagnosed as vasculitis, the absence of hallmark features of vasculitis such as neutrophilic infiltrate of blood vessel walls and fibrinoid necrosis suggest the diagnosis. Extensive laboratory evaluation for inherited and acquired coagulation abnormalities should be performed.

Treatment of LV is difficult, as there is currently no consensus on optimal therapy. The mainstay of therapy is to reduce pain, prevent infection, and reduce ulceration and development of atrophie blanche. Underlying causes should be identified and appropriately treated. Because the primary pathogenesis of LV is considered to be a hypercoagulable state, first-line treatment often includes therapies to enhance blood flow and prevent thrombosis such as smoking cessation, antiplatelet therapy, and pentoxifylline. Vasodilating agents, anti-inflammatory agents, anticoagulation, and fibrinolytic therapy also have been used with varying degrees of success.⁷