Case Reports

Paraneoplastic Isaacs syndrome is a rare disorder with distinct clinical and electromyographic characteristics. It is a consequence of neoplastic process that is not directly caused by the tumor itself, but usually mediated by immune response primarily against the tumor and neural tissues are damaged owing to bystander effect. Paraneoplastic neurologic disorders may precede cancer diagnosis. Here we report the case of 75-year-old woman who presented with numbness, tingling sensation, and weakness of lower extremities, and was diagnosed with Isaacs syndrome and subsequently small-cell lung cancer. Plasmapheresis and treatment of small-cell lung cancer produced signficant symptoms improvement. We also conduct a complete review of the published case reports and case series of Isaacs syndrome of paraneoplastic etiology, which usually has good response to carbamazepine and to specfic treatment of underlying neoplasm. 

Click on the PDF icon at the top of this introduction to read the full article.

Paraneoplastic Isaacs syndrome is a rare disorder with distinct clinical and electromyographic characteristics. It is a consequence of neoplastic process that is not directly caused by the tumor itself, but usually mediated by immune response primarily against the tumor and neural tissues are damaged owing to bystander effect. Paraneoplastic neurologic disorders may precede cancer diagnosis. Here we report the case of 75-year-old woman who presented with numbness, tingling sensation, and weakness of lower extremities, and was diagnosed with Isaacs syndrome and subsequently small-cell lung cancer. Plasmapheresis and treatment of small-cell lung cancer produced signficant symptoms improvement. We also conduct a complete review of the published case reports and case series of Isaacs syndrome of paraneoplastic etiology, which usually has good response to carbamazepine and to specfic treatment of underlying neoplasm. 

Click on the PDF icon at the top of this introduction to read the full article.

Paraneoplastic Isaacs syndrome is a rare disorder with distinct clinical and electromyographic characteristics. It is a consequence of neoplastic process that is not directly caused by the tumor itself, but usually mediated by immune response primarily against the tumor and neural tissues are damaged owing to bystander effect. Paraneoplastic neurologic disorders may precede cancer diagnosis. Here we report the case of 75-year-old woman who presented with numbness, tingling sensation, and weakness of lower extremities, and was diagnosed with Isaacs syndrome and subsequently small-cell lung cancer. Plasmapheresis and treatment of small-cell lung cancer produced signficant symptoms improvement. We also conduct a complete review of the published case reports and case series of Isaacs syndrome of paraneoplastic etiology, which usually has good response to carbamazepine and to specfic treatment of underlying neoplasm. 

Click on the PDF icon at the top of this introduction to read the full article.

Differentiation between a primary adnexal carcinoma and a metastatic carcinoma to the skin is a challenging yet critical task for dermatologists and pathologists. Carcinomas that have metastasized to the skin are a sign of widespread systemic involvement and poor prognosis, while primary adnexal carcinomas tend to progress with an indolent clinical course. Although many patients with cutaneous metastases from an internal primary neoplasm can expect a median survival of no more than 12 months,¹ patients with primary adnexal carcinomas are reported to have a 5-year survival rate of 95.5% for localized disease and 85% with spread to regional lymph nodes.² We report a case of multiple cutaneous neoplasms of unknown primary origin in a 71-year-old man and describe our approach to identification of the possible primary site as well as management of the disease.  

Case Report

A 71-year-old man initially presented to his primary physician for evaluation of a mass on the left side of the neck of 3 months' duration. On physical examination, a firm 2.5×3.0-cm nodule was noted at the anterior border of the trapezius muscle. Palpation of the thyroid revealed an additional right-sided nodule. The submandibular and parotid glands were unremarkable to palpation. The patient was referred to general surgery for biopsy, which revealed an infiltrating, moderately differentiated adenocarcinoma with extensive lymphatic permeation. Immunohistochemical staining for cytokeratin (CK) 7 was positive, while CK20 and thyroid transcription factor 1 were negative. A positron emission tomography/computed tomography (CT) fusion scan demonstrated 3 areas of enhanced uptake: one in the right side of the thyroid, a second corresponding to the mass on the left side of the neck at the level of the trapezius muscle, and a third in the left masseter muscle. Surgical excision with negative margins with possible chemotherapy was recommended; however, the patient declined treatment and was lost to follow-up until 2 years later when he presented to his primary physician with an additional lesion on his scalp.

Four years after the biopsy, the patient presented to the dermatology department with additional tumor nodules including a 4-cm, annular, indurated, focally eroded plaque on the left side of the lateral neck (Figure 1); 3 separate 1-cm nodules on the right side of the lateral neck; and an ulcerated, crusted, 10×8-cm plaque on the posterior aspect of the scalp. Despite the extensive lesions, the patient remained in good health and reported no recent weight loss or signs or symptoms of systemic involvement. The posterior scalp lesion, which developed 2 years after the initial appearance of the mass on the neck and was thought to represent a possible metastasis of the tumor, was biopsied and showed diffuse infiltration of the dermis by poorly differentiated tumor cells with vacuolated cytoplasm arranged in nests and cords and sometimes in a single-file arrangement (Figure 2). A CT scan demonstrated pretracheal lymphadenopathy as well as small intraparenchymal and subpleural pulmonary nodules throughout both lung fields.

Another scalp biopsy was taken. Tumor cells were negative on mucicarmine staining. Additional immunohistochemical staining, including a periodic acid-Schiff stain with diastase digestion for epithelial mucin revealed minimal luminal positivity. Immunostaining was positive for CK7, carcinoembryonic antigen, CD15, estrogen receptor, progesterone receptor, gross cystic disease fluid protein 15 (GCDFP-15), and mammaglobin, and negative for CK20, podoplanin, thyroid transcription factor 1, S-100 protein, p63, and prostate specific antigen. ERBB2 (formerly HER2/neu) staining was negative according to fluorescence in situ hybridization analysis. Tumor cells showed a Ki-67 nuclear proliferation index of greater than 50%, indicating progression to aggressive carcinoma. 

Based on the histological and immunochemical studies, the differential diagnosis included primary cutaneous apocrine carcinoma versus breast carcinoma; however, the prolonged clinical progression of these lesions favored a primary cutaneous adnexal tumor over a metastatic adenocarcinoma. Nevertheless, despite the initially indolent growth of the lesions over the first 5 years, the Ki-67 proliferation index and presence of widespread metastases on the posterior scalp indicated progression to an aggressive carcinoma. Chemotherapy was recommended as the treatment of choice. At his most recent follow-up visit 4 months later, the patient chose to begin treatment with tamoxifen and refused other treatment options.

Comment

The distinction between primary adnexal and metastatic adenocarcinomas of the skin is challenging both clinically and histologically. Some pathologists have argued that metastatic breast carcinomas and primary cutaneous apocrine carcinomas are essentially indistinguishable.³ Patients with cutaneous metastases, which occur in approximately 5.3% of all malignancies,⁴ typically can expect survival of no more than 12 months from the time of detection.¹ In contrast, primary apocrine carcinomas of the skin, though much less common, carry a remarkably better prognosis, with 5-year relative survival rates of 95.5% and 85.5% reported for patients with localized disease and spread to regional lymph nodes, respectively.²

Fewer than 100 cases of primary cutaneous adnexal (apocrine) carcinomas have been reported overall, with the earliest known report dating back to 1944.⁵ According to the literature, primary apocrine carcinomas were diagnosed at a median age of 66 years and were slightly more common in females than males.^2,6 Apocrine carcinomas were seen most frequently on the head, neck, and trunk,² generally presenting in the form of asymptomatic nodules or plaques of 2 to 3 cm in size, with gradual progression occurring over months to years.⁶ Approximately 40% of patients have been reported with positive regional lymph nodes at diagnosis. Treatment of apocrine carcinoma typically has involved local excision with clear margins with or without lymph node dissection. Chemotherapy and radiation therapy have shown no proven benefit.⁷

Currently, there is no standardized approach to evaluating patients with possible cutaneous metastasis versus primary cutaneous adnexal carcinomas. Imaging studies such as mammography and abdominal CT typically reveal an internal primary cancer in one-third of patients. However, additional studies such as gastrointestinal radiography, chest and pelvic CT, barium enema, and intravenous pyelogram have shown to be of limited value.⁸ Although specificity and sensitivity of immunohistochemistry is limited, a number of immunomarkers, including CK7 and CK20, are routinely studied to narrow the differential diagnosis of a cutaneous neoplasm of unclear origin. Urothelial, gastric, colorectal, and pancreatic carcinomas generally are positive for CK20; CK7-positive adenocarcinomas include salivary, non-small cell lung, breast, ovarian, pancreatic, endometrial, and transitional cell adenocarcinomas. Carcinomas negative for both CK7 and CK20 include colorectal, hepatocellular, renal cell, prostate, and squamous cell carcinoma of the lung. 

The presence of positive staining for estrogen and progesterone receptors as well as GCDFP-15 and mammaglobin raised the possibility of primary breast adenocarcinoma in our patient, but given that these markers can be positive in primary cutaneous adnexal tumors, immunohistochemistry results were not able to provide a definitive primary site. The overall staining pattern was nearly identical to 26 cases of primary cutaneous cribriform apocrine carcinoma, which was found to be positive for CK7 and carcinoembryonic antigen, and negative for CK20 and S-100. The only difference was in GCDFP-15 staining, which was positive in our case and negative in the cases of cribriform apocrine carcinoma.⁹ Histologic features favoring a primary apocrine origin include normal apocrine glands in the vicinity, glandular structures with decapitation secretion high in the dermis, and intracytoplasmic iron granules.¹⁰ Additionally, positive estrogen receptor staining appears to be much more common in apocrine carcinomas (5/10) than in eccrine carcinomas (1/7).¹¹

A number of other markers have been investigated for possible diagnostic utility for distinction between primary adnexal carcinomas and metastatic adenocarcinomas. The nuclear transcription factor p63, which plays a role in keratinocyte differentiation, is preferentially expressed in a number of primary adnexal carcinomas and is purported to be the most sensitive marker overall, with a sensitivity of 78% to 91%.^12-14 However, p63 has shown incomplete specificity for primary adnexal neoplasms, having been reported as positive in 11% to 22% of adenocarcinomas metastatic to skin.^15-18 Nestin and CK15, which are expressed in hair follicle progenitor cells, also are potential specific markers for some primary adnexal lesions, specifically eccrine carcinoma, porocarcinoma, hidradenocarcinoma, and microcystic adnexal carcinoma; however, in one report, none of the apocrine carcinomas were positive for p63, cytokeratin 15, or D2-40.¹⁹ Thus, while markers for some primary adnexal neoplasms are emerging, specific tests at the immunohistochemical level for the apocrine carcinoma subgroup are still lacking.

Conclusion

In summary, a conclusive distinction between primary cutaneous apocrine carcinoma and metastatic adenocarcinoma to the skin remains challenging. Although new markers provide more specificity and sensitivity for neoplasms of eccrine origin, these markers do not appear to differentiate between primary apocrine carcinoma and metastatic breast carcinoma. In this case, as in other recent reports, diagnosis remained dependent on the clinical course of the patient. Although considerable progress has been made regarding immunohistochemical analysis of these cases, additional markers, especially ones more specific for primary skin cancers with apocrine differentiation, are still needed.

Differentiation between a primary adnexal carcinoma and a metastatic carcinoma to the skin is a challenging yet critical task for dermatologists and pathologists. Carcinomas that have metastasized to the skin are a sign of widespread systemic involvement and poor prognosis, while primary adnexal carcinomas tend to progress with an indolent clinical course. Although many patients with cutaneous metastases from an internal primary neoplasm can expect a median survival of no more than 12 months,¹ patients with primary adnexal carcinomas are reported to have a 5-year survival rate of 95.5% for localized disease and 85% with spread to regional lymph nodes.² We report a case of multiple cutaneous neoplasms of unknown primary origin in a 71-year-old man and describe our approach to identification of the possible primary site as well as management of the disease.  

Case Report

A 71-year-old man initially presented to his primary physician for evaluation of a mass on the left side of the neck of 3 months' duration. On physical examination, a firm 2.5×3.0-cm nodule was noted at the anterior border of the trapezius muscle. Palpation of the thyroid revealed an additional right-sided nodule. The submandibular and parotid glands were unremarkable to palpation. The patient was referred to general surgery for biopsy, which revealed an infiltrating, moderately differentiated adenocarcinoma with extensive lymphatic permeation. Immunohistochemical staining for cytokeratin (CK) 7 was positive, while CK20 and thyroid transcription factor 1 were negative. A positron emission tomography/computed tomography (CT) fusion scan demonstrated 3 areas of enhanced uptake: one in the right side of the thyroid, a second corresponding to the mass on the left side of the neck at the level of the trapezius muscle, and a third in the left masseter muscle. Surgical excision with negative margins with possible chemotherapy was recommended; however, the patient declined treatment and was lost to follow-up until 2 years later when he presented to his primary physician with an additional lesion on his scalp.

Four years after the biopsy, the patient presented to the dermatology department with additional tumor nodules including a 4-cm, annular, indurated, focally eroded plaque on the left side of the lateral neck (Figure 1); 3 separate 1-cm nodules on the right side of the lateral neck; and an ulcerated, crusted, 10×8-cm plaque on the posterior aspect of the scalp. Despite the extensive lesions, the patient remained in good health and reported no recent weight loss or signs or symptoms of systemic involvement. The posterior scalp lesion, which developed 2 years after the initial appearance of the mass on the neck and was thought to represent a possible metastasis of the tumor, was biopsied and showed diffuse infiltration of the dermis by poorly differentiated tumor cells with vacuolated cytoplasm arranged in nests and cords and sometimes in a single-file arrangement (Figure 2). A CT scan demonstrated pretracheal lymphadenopathy as well as small intraparenchymal and subpleural pulmonary nodules throughout both lung fields.

Another scalp biopsy was taken. Tumor cells were negative on mucicarmine staining. Additional immunohistochemical staining, including a periodic acid-Schiff stain with diastase digestion for epithelial mucin revealed minimal luminal positivity. Immunostaining was positive for CK7, carcinoembryonic antigen, CD15, estrogen receptor, progesterone receptor, gross cystic disease fluid protein 15 (GCDFP-15), and mammaglobin, and negative for CK20, podoplanin, thyroid transcription factor 1, S-100 protein, p63, and prostate specific antigen. ERBB2 (formerly HER2/neu) staining was negative according to fluorescence in situ hybridization analysis. Tumor cells showed a Ki-67 nuclear proliferation index of greater than 50%, indicating progression to aggressive carcinoma. 

Based on the histological and immunochemical studies, the differential diagnosis included primary cutaneous apocrine carcinoma versus breast carcinoma; however, the prolonged clinical progression of these lesions favored a primary cutaneous adnexal tumor over a metastatic adenocarcinoma. Nevertheless, despite the initially indolent growth of the lesions over the first 5 years, the Ki-67 proliferation index and presence of widespread metastases on the posterior scalp indicated progression to an aggressive carcinoma. Chemotherapy was recommended as the treatment of choice. At his most recent follow-up visit 4 months later, the patient chose to begin treatment with tamoxifen and refused other treatment options.

Comment

The distinction between primary adnexal and metastatic adenocarcinomas of the skin is challenging both clinically and histologically. Some pathologists have argued that metastatic breast carcinomas and primary cutaneous apocrine carcinomas are essentially indistinguishable.³ Patients with cutaneous metastases, which occur in approximately 5.3% of all malignancies,⁴ typically can expect survival of no more than 12 months from the time of detection.¹ In contrast, primary apocrine carcinomas of the skin, though much less common, carry a remarkably better prognosis, with 5-year relative survival rates of 95.5% and 85.5% reported for patients with localized disease and spread to regional lymph nodes, respectively.²

Fewer than 100 cases of primary cutaneous adnexal (apocrine) carcinomas have been reported overall, with the earliest known report dating back to 1944.⁵ According to the literature, primary apocrine carcinomas were diagnosed at a median age of 66 years and were slightly more common in females than males.^2,6 Apocrine carcinomas were seen most frequently on the head, neck, and trunk,² generally presenting in the form of asymptomatic nodules or plaques of 2 to 3 cm in size, with gradual progression occurring over months to years.⁶ Approximately 40% of patients have been reported with positive regional lymph nodes at diagnosis. Treatment of apocrine carcinoma typically has involved local excision with clear margins with or without lymph node dissection. Chemotherapy and radiation therapy have shown no proven benefit.⁷

Currently, there is no standardized approach to evaluating patients with possible cutaneous metastasis versus primary cutaneous adnexal carcinomas. Imaging studies such as mammography and abdominal CT typically reveal an internal primary cancer in one-third of patients. However, additional studies such as gastrointestinal radiography, chest and pelvic CT, barium enema, and intravenous pyelogram have shown to be of limited value.⁸ Although specificity and sensitivity of immunohistochemistry is limited, a number of immunomarkers, including CK7 and CK20, are routinely studied to narrow the differential diagnosis of a cutaneous neoplasm of unclear origin. Urothelial, gastric, colorectal, and pancreatic carcinomas generally are positive for CK20; CK7-positive adenocarcinomas include salivary, non-small cell lung, breast, ovarian, pancreatic, endometrial, and transitional cell adenocarcinomas. Carcinomas negative for both CK7 and CK20 include colorectal, hepatocellular, renal cell, prostate, and squamous cell carcinoma of the lung. 

The presence of positive staining for estrogen and progesterone receptors as well as GCDFP-15 and mammaglobin raised the possibility of primary breast adenocarcinoma in our patient, but given that these markers can be positive in primary cutaneous adnexal tumors, immunohistochemistry results were not able to provide a definitive primary site. The overall staining pattern was nearly identical to 26 cases of primary cutaneous cribriform apocrine carcinoma, which was found to be positive for CK7 and carcinoembryonic antigen, and negative for CK20 and S-100. The only difference was in GCDFP-15 staining, which was positive in our case and negative in the cases of cribriform apocrine carcinoma.⁹ Histologic features favoring a primary apocrine origin include normal apocrine glands in the vicinity, glandular structures with decapitation secretion high in the dermis, and intracytoplasmic iron granules.¹⁰ Additionally, positive estrogen receptor staining appears to be much more common in apocrine carcinomas (5/10) than in eccrine carcinomas (1/7).¹¹

A number of other markers have been investigated for possible diagnostic utility for distinction between primary adnexal carcinomas and metastatic adenocarcinomas. The nuclear transcription factor p63, which plays a role in keratinocyte differentiation, is preferentially expressed in a number of primary adnexal carcinomas and is purported to be the most sensitive marker overall, with a sensitivity of 78% to 91%.^12-14 However, p63 has shown incomplete specificity for primary adnexal neoplasms, having been reported as positive in 11% to 22% of adenocarcinomas metastatic to skin.^15-18 Nestin and CK15, which are expressed in hair follicle progenitor cells, also are potential specific markers for some primary adnexal lesions, specifically eccrine carcinoma, porocarcinoma, hidradenocarcinoma, and microcystic adnexal carcinoma; however, in one report, none of the apocrine carcinomas were positive for p63, cytokeratin 15, or D2-40.¹⁹ Thus, while markers for some primary adnexal neoplasms are emerging, specific tests at the immunohistochemical level for the apocrine carcinoma subgroup are still lacking.

Conclusion

In summary, a conclusive distinction between primary cutaneous apocrine carcinoma and metastatic adenocarcinoma to the skin remains challenging. Although new markers provide more specificity and sensitivity for neoplasms of eccrine origin, these markers do not appear to differentiate between primary apocrine carcinoma and metastatic breast carcinoma. In this case, as in other recent reports, diagnosis remained dependent on the clinical course of the patient. Although considerable progress has been made regarding immunohistochemical analysis of these cases, additional markers, especially ones more specific for primary skin cancers with apocrine differentiation, are still needed.

Differentiation between a primary adnexal carcinoma and a metastatic carcinoma to the skin is a challenging yet critical task for dermatologists and pathologists. Carcinomas that have metastasized to the skin are a sign of widespread systemic involvement and poor prognosis, while primary adnexal carcinomas tend to progress with an indolent clinical course. Although many patients with cutaneous metastases from an internal primary neoplasm can expect a median survival of no more than 12 months,¹ patients with primary adnexal carcinomas are reported to have a 5-year survival rate of 95.5% for localized disease and 85% with spread to regional lymph nodes.² We report a case of multiple cutaneous neoplasms of unknown primary origin in a 71-year-old man and describe our approach to identification of the possible primary site as well as management of the disease.  

Case Report

A 71-year-old man initially presented to his primary physician for evaluation of a mass on the left side of the neck of 3 months' duration. On physical examination, a firm 2.5×3.0-cm nodule was noted at the anterior border of the trapezius muscle. Palpation of the thyroid revealed an additional right-sided nodule. The submandibular and parotid glands were unremarkable to palpation. The patient was referred to general surgery for biopsy, which revealed an infiltrating, moderately differentiated adenocarcinoma with extensive lymphatic permeation. Immunohistochemical staining for cytokeratin (CK) 7 was positive, while CK20 and thyroid transcription factor 1 were negative. A positron emission tomography/computed tomography (CT) fusion scan demonstrated 3 areas of enhanced uptake: one in the right side of the thyroid, a second corresponding to the mass on the left side of the neck at the level of the trapezius muscle, and a third in the left masseter muscle. Surgical excision with negative margins with possible chemotherapy was recommended; however, the patient declined treatment and was lost to follow-up until 2 years later when he presented to his primary physician with an additional lesion on his scalp.

Four years after the biopsy, the patient presented to the dermatology department with additional tumor nodules including a 4-cm, annular, indurated, focally eroded plaque on the left side of the lateral neck (Figure 1); 3 separate 1-cm nodules on the right side of the lateral neck; and an ulcerated, crusted, 10×8-cm plaque on the posterior aspect of the scalp. Despite the extensive lesions, the patient remained in good health and reported no recent weight loss or signs or symptoms of systemic involvement. The posterior scalp lesion, which developed 2 years after the initial appearance of the mass on the neck and was thought to represent a possible metastasis of the tumor, was biopsied and showed diffuse infiltration of the dermis by poorly differentiated tumor cells with vacuolated cytoplasm arranged in nests and cords and sometimes in a single-file arrangement (Figure 2). A CT scan demonstrated pretracheal lymphadenopathy as well as small intraparenchymal and subpleural pulmonary nodules throughout both lung fields.

Another scalp biopsy was taken. Tumor cells were negative on mucicarmine staining. Additional immunohistochemical staining, including a periodic acid-Schiff stain with diastase digestion for epithelial mucin revealed minimal luminal positivity. Immunostaining was positive for CK7, carcinoembryonic antigen, CD15, estrogen receptor, progesterone receptor, gross cystic disease fluid protein 15 (GCDFP-15), and mammaglobin, and negative for CK20, podoplanin, thyroid transcription factor 1, S-100 protein, p63, and prostate specific antigen. ERBB2 (formerly HER2/neu) staining was negative according to fluorescence in situ hybridization analysis. Tumor cells showed a Ki-67 nuclear proliferation index of greater than 50%, indicating progression to aggressive carcinoma. 

Based on the histological and immunochemical studies, the differential diagnosis included primary cutaneous apocrine carcinoma versus breast carcinoma; however, the prolonged clinical progression of these lesions favored a primary cutaneous adnexal tumor over a metastatic adenocarcinoma. Nevertheless, despite the initially indolent growth of the lesions over the first 5 years, the Ki-67 proliferation index and presence of widespread metastases on the posterior scalp indicated progression to an aggressive carcinoma. Chemotherapy was recommended as the treatment of choice. At his most recent follow-up visit 4 months later, the patient chose to begin treatment with tamoxifen and refused other treatment options.

Comment

The distinction between primary adnexal and metastatic adenocarcinomas of the skin is challenging both clinically and histologically. Some pathologists have argued that metastatic breast carcinomas and primary cutaneous apocrine carcinomas are essentially indistinguishable.³ Patients with cutaneous metastases, which occur in approximately 5.3% of all malignancies,⁴ typically can expect survival of no more than 12 months from the time of detection.¹ In contrast, primary apocrine carcinomas of the skin, though much less common, carry a remarkably better prognosis, with 5-year relative survival rates of 95.5% and 85.5% reported for patients with localized disease and spread to regional lymph nodes, respectively.²

Fewer than 100 cases of primary cutaneous adnexal (apocrine) carcinomas have been reported overall, with the earliest known report dating back to 1944.⁵ According to the literature, primary apocrine carcinomas were diagnosed at a median age of 66 years and were slightly more common in females than males.^2,6 Apocrine carcinomas were seen most frequently on the head, neck, and trunk,² generally presenting in the form of asymptomatic nodules or plaques of 2 to 3 cm in size, with gradual progression occurring over months to years.⁶ Approximately 40% of patients have been reported with positive regional lymph nodes at diagnosis. Treatment of apocrine carcinoma typically has involved local excision with clear margins with or without lymph node dissection. Chemotherapy and radiation therapy have shown no proven benefit.⁷

Currently, there is no standardized approach to evaluating patients with possible cutaneous metastasis versus primary cutaneous adnexal carcinomas. Imaging studies such as mammography and abdominal CT typically reveal an internal primary cancer in one-third of patients. However, additional studies such as gastrointestinal radiography, chest and pelvic CT, barium enema, and intravenous pyelogram have shown to be of limited value.⁸ Although specificity and sensitivity of immunohistochemistry is limited, a number of immunomarkers, including CK7 and CK20, are routinely studied to narrow the differential diagnosis of a cutaneous neoplasm of unclear origin. Urothelial, gastric, colorectal, and pancreatic carcinomas generally are positive for CK20; CK7-positive adenocarcinomas include salivary, non-small cell lung, breast, ovarian, pancreatic, endometrial, and transitional cell adenocarcinomas. Carcinomas negative for both CK7 and CK20 include colorectal, hepatocellular, renal cell, prostate, and squamous cell carcinoma of the lung. 

The presence of positive staining for estrogen and progesterone receptors as well as GCDFP-15 and mammaglobin raised the possibility of primary breast adenocarcinoma in our patient, but given that these markers can be positive in primary cutaneous adnexal tumors, immunohistochemistry results were not able to provide a definitive primary site. The overall staining pattern was nearly identical to 26 cases of primary cutaneous cribriform apocrine carcinoma, which was found to be positive for CK7 and carcinoembryonic antigen, and negative for CK20 and S-100. The only difference was in GCDFP-15 staining, which was positive in our case and negative in the cases of cribriform apocrine carcinoma.⁹ Histologic features favoring a primary apocrine origin include normal apocrine glands in the vicinity, glandular structures with decapitation secretion high in the dermis, and intracytoplasmic iron granules.¹⁰ Additionally, positive estrogen receptor staining appears to be much more common in apocrine carcinomas (5/10) than in eccrine carcinomas (1/7).¹¹

A number of other markers have been investigated for possible diagnostic utility for distinction between primary adnexal carcinomas and metastatic adenocarcinomas. The nuclear transcription factor p63, which plays a role in keratinocyte differentiation, is preferentially expressed in a number of primary adnexal carcinomas and is purported to be the most sensitive marker overall, with a sensitivity of 78% to 91%.^12-14 However, p63 has shown incomplete specificity for primary adnexal neoplasms, having been reported as positive in 11% to 22% of adenocarcinomas metastatic to skin.^15-18 Nestin and CK15, which are expressed in hair follicle progenitor cells, also are potential specific markers for some primary adnexal lesions, specifically eccrine carcinoma, porocarcinoma, hidradenocarcinoma, and microcystic adnexal carcinoma; however, in one report, none of the apocrine carcinomas were positive for p63, cytokeratin 15, or D2-40.¹⁹ Thus, while markers for some primary adnexal neoplasms are emerging, specific tests at the immunohistochemical level for the apocrine carcinoma subgroup are still lacking.

Conclusion

In summary, a conclusive distinction between primary cutaneous apocrine carcinoma and metastatic adenocarcinoma to the skin remains challenging. Although new markers provide more specificity and sensitivity for neoplasms of eccrine origin, these markers do not appear to differentiate between primary apocrine carcinoma and metastatic breast carcinoma. In this case, as in other recent reports, diagnosis remained dependent on the clinical course of the patient. Although considerable progress has been made regarding immunohistochemical analysis of these cases, additional markers, especially ones more specific for primary skin cancers with apocrine differentiation, are still needed.

Approximately 600 cases of operating room (OR) fires are reported annually.¹ The incidence of OR fires in the United States equals that of wrong-site surgeries, and 20% of cases have associated morbidity.^1,2 The estimated mortality rate is 1 to 2 cases per year.^3-5 The most commonly involved anatomical regions are the airway (33%) and the face (28%).⁴ Most surgical fires are reported in anesthetized patients with open oxygen delivery systems during head, neck, and upper chest surgeries; electrosurgical instruments are the ignition source in 90% of these cases.⁶ Despite extensive fire safety education and training, complete elimination of OR fires still has not been achieved.

Each fire requires an ignition source, a fuel source, and an oxidizer.⁷ In the OR, the 2 most common oxidizers are oxygen and nitrous oxide. Head and neck surgeries have a high concentration of these gases near the working field and therefore a higher risk and incidence of fires. Furthermore, surgical drapes and equipment (eg, closed or semi-closed breathing systems, masks) may potentiate this risk by reducing ventilation in areas where gases can accumulate and ignite. Ignition sources provide the energy that starts fires; common sources are electrocautery, lasers, fiber-optic light cords, drills/burrs, and defibrillator paddles. Fires are propagated by fuel sources, which encompass any flammable material, including tracheal tubes, sponges, alcohol-based solutions, hair, gastrointestinal tract gases, gloves, and packaging materials.⁸ Of note, alcohol-based skin-preparation agents emit flammable vapors that can ignite.^9-14 Before draping or exposure to an ignition source, chlorhexidine gluconate-based preparations must be allowed to dry for at least 3 minutes after application to hairless skin and up to 1 hour after application to hair.¹⁵ Inadequate drying poses a risk of fire.¹⁰We present the case of an OR fire ignited by electrocautery near freshly applied bone cement. No patient information is disclosed in this report.

Case Report

Our patient was evaluated in clinic and scheduled for total knee arthroplasty (TKA). All preoperative safety checklists and time-out procedures were followed and documented at the start of surgery. The TKA was performed with a standard medial patellar arthrotomy. Tourniquet control was used after Esmarch exsanguination. The surgery proceeded uneventfully until just after the bone cement was applied to the tibial surface. The surgeon was using a Bovie to resect residual lateral meniscus tissue when a fire instantaneously erupted within the joint space. Fortunately, the surgeon quickly suffocated the fire with a dry towel. The ignited bone cement was removed, and the patient was examined. There was no injury to surrounding tissue or joint space. Surgery was resumed with application of new bone cement to the tibial surface. The artificial joint was then successfully implanted and the case completed without further incident. The patient was discharged from the hospital and followed up as an outpatient without any postoperative complications.

Discussion

Bone cement, which is commonly used in artificial joint anchoring, craniofacial reconstruction, and vertebroplasty, has liquid and powder components. The liquid monomer methyl methacrylate (MMA) is colorless and flammable and has a distinct odor.¹⁶ Exposure to heat or light can prematurely polymerize MMA, requiring the addition of hydroquinone to inhibit the reaction.¹⁶ The powder polymethylmethacrylate affords excellent structural support, radiopacity, and facility of use.¹⁷ Dibenzoyl peroxide and N,N-dimethyl-p-toluidine are added to the powder to facilitate the polymerization reaction at room temperature (ie, cold curing of cement). Premature application of unpolymerized cement increases the risk of fire from the volatile liquid component.

In the OR, bone cement is prepared by mixing together its powder and liquid components.¹⁸ The reaction is exothermic polymerization. The liquid is highly volatile and flammable in both liquid and vapor states.^16,19 The vapors are denser than air and can concentrate in poorly ventilated areas. The OR and the application site must be adequately ventilated to eliminate any pockets of vapor accumulation.¹⁶ A vacuum mixer can be used to minimize fume exposure, enhance cement strength, and reduce fire risk while combining the 2 components.

MMA’s flash point, the temperature at which the fumes could ignite in the presence of an ignition source, is 10.5ºC. The auto-ignition point, the temperature at which MMA spontaneously combusts, is 421ºC.²⁰ The OR is usually warmer than the flash point temperature, but the electrocautery tip can generate up to 1200ºC of heat.²¹ Therefore, bone cement is a potential fire hazard, and use of Bovies or other ignition sources in its vicinity must be avoided.

The Table lists the recommended times for preparing various bone cement products.^22,23Mix time is the time needed to combine the liquid and powder into a homogenous putty.

Approximately 600 cases of operating room (OR) fires are reported annually.¹ The incidence of OR fires in the United States equals that of wrong-site surgeries, and 20% of cases have associated morbidity.^1,2 The estimated mortality rate is 1 to 2 cases per year.^3-5 The most commonly involved anatomical regions are the airway (33%) and the face (28%).⁴ Most surgical fires are reported in anesthetized patients with open oxygen delivery systems during head, neck, and upper chest surgeries; electrosurgical instruments are the ignition source in 90% of these cases.⁶ Despite extensive fire safety education and training, complete elimination of OR fires still has not been achieved.

Each fire requires an ignition source, a fuel source, and an oxidizer.⁷ In the OR, the 2 most common oxidizers are oxygen and nitrous oxide. Head and neck surgeries have a high concentration of these gases near the working field and therefore a higher risk and incidence of fires. Furthermore, surgical drapes and equipment (eg, closed or semi-closed breathing systems, masks) may potentiate this risk by reducing ventilation in areas where gases can accumulate and ignite. Ignition sources provide the energy that starts fires; common sources are electrocautery, lasers, fiber-optic light cords, drills/burrs, and defibrillator paddles. Fires are propagated by fuel sources, which encompass any flammable material, including tracheal tubes, sponges, alcohol-based solutions, hair, gastrointestinal tract gases, gloves, and packaging materials.⁸ Of note, alcohol-based skin-preparation agents emit flammable vapors that can ignite.^9-14 Before draping or exposure to an ignition source, chlorhexidine gluconate-based preparations must be allowed to dry for at least 3 minutes after application to hairless skin and up to 1 hour after application to hair.¹⁵ Inadequate drying poses a risk of fire.¹⁰We present the case of an OR fire ignited by electrocautery near freshly applied bone cement. No patient information is disclosed in this report.

Case Report

Our patient was evaluated in clinic and scheduled for total knee arthroplasty (TKA). All preoperative safety checklists and time-out procedures were followed and documented at the start of surgery. The TKA was performed with a standard medial patellar arthrotomy. Tourniquet control was used after Esmarch exsanguination. The surgery proceeded uneventfully until just after the bone cement was applied to the tibial surface. The surgeon was using a Bovie to resect residual lateral meniscus tissue when a fire instantaneously erupted within the joint space. Fortunately, the surgeon quickly suffocated the fire with a dry towel. The ignited bone cement was removed, and the patient was examined. There was no injury to surrounding tissue or joint space. Surgery was resumed with application of new bone cement to the tibial surface. The artificial joint was then successfully implanted and the case completed without further incident. The patient was discharged from the hospital and followed up as an outpatient without any postoperative complications.

Discussion

Bone cement, which is commonly used in artificial joint anchoring, craniofacial reconstruction, and vertebroplasty, has liquid and powder components. The liquid monomer methyl methacrylate (MMA) is colorless and flammable and has a distinct odor.¹⁶ Exposure to heat or light can prematurely polymerize MMA, requiring the addition of hydroquinone to inhibit the reaction.¹⁶ The powder polymethylmethacrylate affords excellent structural support, radiopacity, and facility of use.¹⁷ Dibenzoyl peroxide and N,N-dimethyl-p-toluidine are added to the powder to facilitate the polymerization reaction at room temperature (ie, cold curing of cement). Premature application of unpolymerized cement increases the risk of fire from the volatile liquid component.

In the OR, bone cement is prepared by mixing together its powder and liquid components.¹⁸ The reaction is exothermic polymerization. The liquid is highly volatile and flammable in both liquid and vapor states.^16,19 The vapors are denser than air and can concentrate in poorly ventilated areas. The OR and the application site must be adequately ventilated to eliminate any pockets of vapor accumulation.¹⁶ A vacuum mixer can be used to minimize fume exposure, enhance cement strength, and reduce fire risk while combining the 2 components.

MMA’s flash point, the temperature at which the fumes could ignite in the presence of an ignition source, is 10.5ºC. The auto-ignition point, the temperature at which MMA spontaneously combusts, is 421ºC.²⁰ The OR is usually warmer than the flash point temperature, but the electrocautery tip can generate up to 1200ºC of heat.²¹ Therefore, bone cement is a potential fire hazard, and use of Bovies or other ignition sources in its vicinity must be avoided.

The Table lists the recommended times for preparing various bone cement products.^22,23Mix time is the time needed to combine the liquid and powder into a homogenous putty.

Approximately 600 cases of operating room (OR) fires are reported annually.¹ The incidence of OR fires in the United States equals that of wrong-site surgeries, and 20% of cases have associated morbidity.^1,2 The estimated mortality rate is 1 to 2 cases per year.^3-5 The most commonly involved anatomical regions are the airway (33%) and the face (28%).⁴ Most surgical fires are reported in anesthetized patients with open oxygen delivery systems during head, neck, and upper chest surgeries; electrosurgical instruments are the ignition source in 90% of these cases.⁶ Despite extensive fire safety education and training, complete elimination of OR fires still has not been achieved.

Each fire requires an ignition source, a fuel source, and an oxidizer.⁷ In the OR, the 2 most common oxidizers are oxygen and nitrous oxide. Head and neck surgeries have a high concentration of these gases near the working field and therefore a higher risk and incidence of fires. Furthermore, surgical drapes and equipment (eg, closed or semi-closed breathing systems, masks) may potentiate this risk by reducing ventilation in areas where gases can accumulate and ignite. Ignition sources provide the energy that starts fires; common sources are electrocautery, lasers, fiber-optic light cords, drills/burrs, and defibrillator paddles. Fires are propagated by fuel sources, which encompass any flammable material, including tracheal tubes, sponges, alcohol-based solutions, hair, gastrointestinal tract gases, gloves, and packaging materials.⁸ Of note, alcohol-based skin-preparation agents emit flammable vapors that can ignite.^9-14 Before draping or exposure to an ignition source, chlorhexidine gluconate-based preparations must be allowed to dry for at least 3 minutes after application to hairless skin and up to 1 hour after application to hair.¹⁵ Inadequate drying poses a risk of fire.¹⁰We present the case of an OR fire ignited by electrocautery near freshly applied bone cement. No patient information is disclosed in this report.

Case Report

Our patient was evaluated in clinic and scheduled for total knee arthroplasty (TKA). All preoperative safety checklists and time-out procedures were followed and documented at the start of surgery. The TKA was performed with a standard medial patellar arthrotomy. Tourniquet control was used after Esmarch exsanguination. The surgery proceeded uneventfully until just after the bone cement was applied to the tibial surface. The surgeon was using a Bovie to resect residual lateral meniscus tissue when a fire instantaneously erupted within the joint space. Fortunately, the surgeon quickly suffocated the fire with a dry towel. The ignited bone cement was removed, and the patient was examined. There was no injury to surrounding tissue or joint space. Surgery was resumed with application of new bone cement to the tibial surface. The artificial joint was then successfully implanted and the case completed without further incident. The patient was discharged from the hospital and followed up as an outpatient without any postoperative complications.

Discussion

Bone cement, which is commonly used in artificial joint anchoring, craniofacial reconstruction, and vertebroplasty, has liquid and powder components. The liquid monomer methyl methacrylate (MMA) is colorless and flammable and has a distinct odor.¹⁶ Exposure to heat or light can prematurely polymerize MMA, requiring the addition of hydroquinone to inhibit the reaction.¹⁶ The powder polymethylmethacrylate affords excellent structural support, radiopacity, and facility of use.¹⁷ Dibenzoyl peroxide and N,N-dimethyl-p-toluidine are added to the powder to facilitate the polymerization reaction at room temperature (ie, cold curing of cement). Premature application of unpolymerized cement increases the risk of fire from the volatile liquid component.

In the OR, bone cement is prepared by mixing together its powder and liquid components.¹⁸ The reaction is exothermic polymerization. The liquid is highly volatile and flammable in both liquid and vapor states.^16,19 The vapors are denser than air and can concentrate in poorly ventilated areas. The OR and the application site must be adequately ventilated to eliminate any pockets of vapor accumulation.¹⁶ A vacuum mixer can be used to minimize fume exposure, enhance cement strength, and reduce fire risk while combining the 2 components.

MMA’s flash point, the temperature at which the fumes could ignite in the presence of an ignition source, is 10.5ºC. The auto-ignition point, the temperature at which MMA spontaneously combusts, is 421ºC.²⁰ The OR is usually warmer than the flash point temperature, but the electrocautery tip can generate up to 1200ºC of heat.²¹ Therefore, bone cement is a potential fire hazard, and use of Bovies or other ignition sources in its vicinity must be avoided.

The Table lists the recommended times for preparing various bone cement products.^22,23Mix time is the time needed to combine the liquid and powder into a homogenous putty.

Keratoacanthomas (KAs) are rapidly growing tumors most prominently found on sun-exposed areas of the skin. The normal progression of a KA is to show rapid growth followed by spontaneous resolution.¹ Most KAs are solitary; however, there are several variants of multiple KAs including the familial Ferguson-Smith type, Gryzbowski syndrome (generalized eruptive KAs), KA centrifugum marginatum, Muir-Torre syndrome, and xeroderma pigmentosum.^2-4 Keratoacanthomas also may develop in areas of trauma, including burns, laser treatment, radiation, and surgical margins from excisional biopsies or skin grafting.⁵ Treatment of multiple KAs can be difficult due to a potentially large field size and number of lesions.⁶ We present a case of multiple KAs developing both in the surgical margins and de novo that responded dramatically to treatment with intralesional methotrexate (MTX).

Case Report

A 55-year-old man with a history of a surgically treated squamous cell carcinoma (SCC) on the anterior aspect of the right leg developed multiple nodules involving the surgical scar. He previously underwent Mohs micrographic surgery (MMS); within a month after the second surgery the patient noticed increased pruritus along with scaly pink changes at the site of the surgical scar.

One month prior to presentation, biopsies from the anterior aspect of the right leg demonstrated well-differentiated SCC and he was subsequently treated with MMS; however, examination 1 month after MMS revealed an 11×7-cm indurated plaque with multiple nodules ranging from 1 to 2 cm near the periphery of the plaque with central atrophy and scarring, reminiscent of KA centrifugum marginatum (Figure, A). In a similar fashion, an 8×5-cm plaque composed of 7 nodular areas was noted on the posterior aspect of the right leg (Figure, B). The patient denied any history of trauma to this area. There was no palpable regional lymphadenopathy and the remainder of the skin examination was normal, except for signs of venous stasis in both legs.

Based on the location and morphology of the lesions, the clinical presentation was consistent with multiple KAs. Histologic examination from punch biopsies taken from the plaque's periphery demonstrated well-differentiated SCC (KA type), as well as a lichenoid inflammatory process, epidermal hyperplasia, and cystic and endophytic squamous proliferation suggestive of hypertrophic lichen planus (HLP).

In consideration of the size and number of the lesions as well as the prolonged wound healing with prior surgery, the patient consented to treatment with intralesional MTX (1 mL of 12.5 mg/mL every 2 weeks) rather than undergoing further surgery. The MTX injection was distributed between the lesions on the anterior and posterior aspects of the lower right leg. At each injection session, the size, thickness, and nodularity of the tumor decreased with markedly less pruritus and symptomatic relief was achieved. After 3 injection sessions, resulting in a total of 3 mL of 12.5 mg/mL of MTX, biopsies were taken from the residual atrophic scar on the anterior aspect of the right leg and the remaining 3 papules on the posterior aspect of the right leg to rule out HLP and invasive SCC. The pathology report commented on the presence of prurigo nodules without any evidence of SCC.

At 3-month follow-up, the patient demonstrated no new lesions or recurrence (Figure, C and D). The right leg continued to heal with scarring and postinflammatory pigmentary changes. The patient was monitored for recurrence and to determine the diagnosis of HLP.

Comment

We report the development of multiple KAs arising both from within surgical margins and de novo, and resolution with intralesional MTX. Keratoacanthomas, especially various KA types, have been observed to develop due to various types of trauma, including sites of surgical scars, lichen planus, tattoos, thermal burns, radiation, and discoid lupus erythematosus, and within skin grafts and donor sites.^5-19

Hypertrophic lichen planus is a chronic variant of lichen planus that often is found on the pretibial areas of the lower legs.¹³ Both SCC and reactive KAs have been observed to develop within lesions of HLP.¹⁴ Our pathologist commented on the presence of a lichenoid infiltrate with necrotic keratinocytes and epidermal hyperplasia suspicious for HLP, with a small focus of cystic and endophytic squamous proliferation. The latter lacked notable atypia or an invasive component and could represent an irritated infundibular cyst versus an early evolving KA.

The lichenoid inflammation is suspicious for HLP, which has been associated with eruptive KAs^13-16 and may have contributed to the development of persistent KAs in our patient, both in sites of surgical scars (the anterior aspect of the leg) and in uninvolved skin (the posterior aspect of the leg). Trauma from the prior surgery may have stimulated a local inflammatory response and, if coupled with a preexisting underlying chronic inflammatory condition such as HLP, may have triggered the development of new lesions on the posterior leg. Skin pathergy reactions also are caused by an upregulated inflammatory response, which is reduced with immunosuppressive agents such as MTX.¹²

In our patient, there was both an isotopic and isomorphic response. The term isotopic response refers to the occurrence of a new skin disorder at the site of another unrelated and already healed skin disease. It was first defined by Wolf and Wolf²⁰ in 1985 and hence is also known as Wolf isotopic response. The isotopic response in our patient occurred in the setting of lichen planus. The isomorphic response indicates the appearance of typical skin lesions of an existing dermatosis at sites of other skin injuries.

Initially, we thought the patient had recurrence of SCC, but with the rapid development of multiple lesions, the diagnosis of multiple KAs was more likely. Kimyai-Asadi et al⁸ demonstrated that surgical trauma can precede the development of KAs, as they reported a patient who developed a KA at an excision site. Tamir et al⁷ reported the simultaneous appearance of KAs in burn scars and skin graft donor sites 4 months after a 40% total body surface area burn. Hamilton et al¹¹ described surgical trauma from a split-skin graft donor site as a trigger for the onset of a KA.

Multiple treatment alternatives exist for KAs, with the standard of care for large or high-risk KAs being excisional surgery^21,22; however, other approaches may need to be considered in certain cases, such as with multiple KAs in which lesions may be large and extensive, thereby yielding poor cosmetic outcomes, or with increased surgical risk.²³ Furthermore, multiple KAs that develop in the setting of surgical scars require special consideration. Topical 5-fluorouracil, various systemic and intralesional agents (eg, retinoids, interferon, bleomycin, MTX), laser therapy, electrodesiccation and curettage, radiotherapy, and photodynamic therapy all have been reported as methods employed for the treatment of KA.^23-27 Goldberg et al⁵ reported cases of resolution of eruptive KAs arising in both surgical and nonsurgical sites with a combination of deep shave excision, MMS, curettage and desiccation, and oral isotretinoin.

For our patient, we opted for treatment with intralesional MTX, both due to its effectiveness for solitary KAs and reasonably decreased risk of morbidity compared to surgical excision of regions of the pretibial calves. Treatment with MTX would not have been attempted if there was any clinical doubt that the lesions were not the well-differentiated KA type. Also, we had a low threshold for discontinuing therapy and reverting to MMS treatment if any of the lesions displayed a paradoxical growth post-MTX treatment or failed to respond after 3 treatments. Intralesional MTX is less invasive, relatively inexpensive, and a treatment modality with decreased morbidity for KAs, especially for multiple KAs. It should be considered as a potential alternative to surgery in such cases.^23-27

Keratoacanthomas (KAs) are rapidly growing tumors most prominently found on sun-exposed areas of the skin. The normal progression of a KA is to show rapid growth followed by spontaneous resolution.¹ Most KAs are solitary; however, there are several variants of multiple KAs including the familial Ferguson-Smith type, Gryzbowski syndrome (generalized eruptive KAs), KA centrifugum marginatum, Muir-Torre syndrome, and xeroderma pigmentosum.^2-4 Keratoacanthomas also may develop in areas of trauma, including burns, laser treatment, radiation, and surgical margins from excisional biopsies or skin grafting.⁵ Treatment of multiple KAs can be difficult due to a potentially large field size and number of lesions.⁶ We present a case of multiple KAs developing both in the surgical margins and de novo that responded dramatically to treatment with intralesional methotrexate (MTX).

Case Report

A 55-year-old man with a history of a surgically treated squamous cell carcinoma (SCC) on the anterior aspect of the right leg developed multiple nodules involving the surgical scar. He previously underwent Mohs micrographic surgery (MMS); within a month after the second surgery the patient noticed increased pruritus along with scaly pink changes at the site of the surgical scar.

One month prior to presentation, biopsies from the anterior aspect of the right leg demonstrated well-differentiated SCC and he was subsequently treated with MMS; however, examination 1 month after MMS revealed an 11×7-cm indurated plaque with multiple nodules ranging from 1 to 2 cm near the periphery of the plaque with central atrophy and scarring, reminiscent of KA centrifugum marginatum (Figure, A). In a similar fashion, an 8×5-cm plaque composed of 7 nodular areas was noted on the posterior aspect of the right leg (Figure, B). The patient denied any history of trauma to this area. There was no palpable regional lymphadenopathy and the remainder of the skin examination was normal, except for signs of venous stasis in both legs.

Based on the location and morphology of the lesions, the clinical presentation was consistent with multiple KAs. Histologic examination from punch biopsies taken from the plaque's periphery demonstrated well-differentiated SCC (KA type), as well as a lichenoid inflammatory process, epidermal hyperplasia, and cystic and endophytic squamous proliferation suggestive of hypertrophic lichen planus (HLP).

In consideration of the size and number of the lesions as well as the prolonged wound healing with prior surgery, the patient consented to treatment with intralesional MTX (1 mL of 12.5 mg/mL every 2 weeks) rather than undergoing further surgery. The MTX injection was distributed between the lesions on the anterior and posterior aspects of the lower right leg. At each injection session, the size, thickness, and nodularity of the tumor decreased with markedly less pruritus and symptomatic relief was achieved. After 3 injection sessions, resulting in a total of 3 mL of 12.5 mg/mL of MTX, biopsies were taken from the residual atrophic scar on the anterior aspect of the right leg and the remaining 3 papules on the posterior aspect of the right leg to rule out HLP and invasive SCC. The pathology report commented on the presence of prurigo nodules without any evidence of SCC.

At 3-month follow-up, the patient demonstrated no new lesions or recurrence (Figure, C and D). The right leg continued to heal with scarring and postinflammatory pigmentary changes. The patient was monitored for recurrence and to determine the diagnosis of HLP.

Comment

We report the development of multiple KAs arising both from within surgical margins and de novo, and resolution with intralesional MTX. Keratoacanthomas, especially various KA types, have been observed to develop due to various types of trauma, including sites of surgical scars, lichen planus, tattoos, thermal burns, radiation, and discoid lupus erythematosus, and within skin grafts and donor sites.^5-19

Hypertrophic lichen planus is a chronic variant of lichen planus that often is found on the pretibial areas of the lower legs.¹³ Both SCC and reactive KAs have been observed to develop within lesions of HLP.¹⁴ Our pathologist commented on the presence of a lichenoid infiltrate with necrotic keratinocytes and epidermal hyperplasia suspicious for HLP, with a small focus of cystic and endophytic squamous proliferation. The latter lacked notable atypia or an invasive component and could represent an irritated infundibular cyst versus an early evolving KA.

The lichenoid inflammation is suspicious for HLP, which has been associated with eruptive KAs^13-16 and may have contributed to the development of persistent KAs in our patient, both in sites of surgical scars (the anterior aspect of the leg) and in uninvolved skin (the posterior aspect of the leg). Trauma from the prior surgery may have stimulated a local inflammatory response and, if coupled with a preexisting underlying chronic inflammatory condition such as HLP, may have triggered the development of new lesions on the posterior leg. Skin pathergy reactions also are caused by an upregulated inflammatory response, which is reduced with immunosuppressive agents such as MTX.¹²

In our patient, there was both an isotopic and isomorphic response. The term isotopic response refers to the occurrence of a new skin disorder at the site of another unrelated and already healed skin disease. It was first defined by Wolf and Wolf²⁰ in 1985 and hence is also known as Wolf isotopic response. The isotopic response in our patient occurred in the setting of lichen planus. The isomorphic response indicates the appearance of typical skin lesions of an existing dermatosis at sites of other skin injuries.

Initially, we thought the patient had recurrence of SCC, but with the rapid development of multiple lesions, the diagnosis of multiple KAs was more likely. Kimyai-Asadi et al⁸ demonstrated that surgical trauma can precede the development of KAs, as they reported a patient who developed a KA at an excision site. Tamir et al⁷ reported the simultaneous appearance of KAs in burn scars and skin graft donor sites 4 months after a 40% total body surface area burn. Hamilton et al¹¹ described surgical trauma from a split-skin graft donor site as a trigger for the onset of a KA.

Multiple treatment alternatives exist for KAs, with the standard of care for large or high-risk KAs being excisional surgery^21,22; however, other approaches may need to be considered in certain cases, such as with multiple KAs in which lesions may be large and extensive, thereby yielding poor cosmetic outcomes, or with increased surgical risk.²³ Furthermore, multiple KAs that develop in the setting of surgical scars require special consideration. Topical 5-fluorouracil, various systemic and intralesional agents (eg, retinoids, interferon, bleomycin, MTX), laser therapy, electrodesiccation and curettage, radiotherapy, and photodynamic therapy all have been reported as methods employed for the treatment of KA.^23-27 Goldberg et al⁵ reported cases of resolution of eruptive KAs arising in both surgical and nonsurgical sites with a combination of deep shave excision, MMS, curettage and desiccation, and oral isotretinoin.

For our patient, we opted for treatment with intralesional MTX, both due to its effectiveness for solitary KAs and reasonably decreased risk of morbidity compared to surgical excision of regions of the pretibial calves. Treatment with MTX would not have been attempted if there was any clinical doubt that the lesions were not the well-differentiated KA type. Also, we had a low threshold for discontinuing therapy and reverting to MMS treatment if any of the lesions displayed a paradoxical growth post-MTX treatment or failed to respond after 3 treatments. Intralesional MTX is less invasive, relatively inexpensive, and a treatment modality with decreased morbidity for KAs, especially for multiple KAs. It should be considered as a potential alternative to surgery in such cases.^23-27

Keratoacanthomas (KAs) are rapidly growing tumors most prominently found on sun-exposed areas of the skin. The normal progression of a KA is to show rapid growth followed by spontaneous resolution.¹ Most KAs are solitary; however, there are several variants of multiple KAs including the familial Ferguson-Smith type, Gryzbowski syndrome (generalized eruptive KAs), KA centrifugum marginatum, Muir-Torre syndrome, and xeroderma pigmentosum.^2-4 Keratoacanthomas also may develop in areas of trauma, including burns, laser treatment, radiation, and surgical margins from excisional biopsies or skin grafting.⁵ Treatment of multiple KAs can be difficult due to a potentially large field size and number of lesions.⁶ We present a case of multiple KAs developing both in the surgical margins and de novo that responded dramatically to treatment with intralesional methotrexate (MTX).

Case Report

A 55-year-old man with a history of a surgically treated squamous cell carcinoma (SCC) on the anterior aspect of the right leg developed multiple nodules involving the surgical scar. He previously underwent Mohs micrographic surgery (MMS); within a month after the second surgery the patient noticed increased pruritus along with scaly pink changes at the site of the surgical scar.

One month prior to presentation, biopsies from the anterior aspect of the right leg demonstrated well-differentiated SCC and he was subsequently treated with MMS; however, examination 1 month after MMS revealed an 11×7-cm indurated plaque with multiple nodules ranging from 1 to 2 cm near the periphery of the plaque with central atrophy and scarring, reminiscent of KA centrifugum marginatum (Figure, A). In a similar fashion, an 8×5-cm plaque composed of 7 nodular areas was noted on the posterior aspect of the right leg (Figure, B). The patient denied any history of trauma to this area. There was no palpable regional lymphadenopathy and the remainder of the skin examination was normal, except for signs of venous stasis in both legs.

Based on the location and morphology of the lesions, the clinical presentation was consistent with multiple KAs. Histologic examination from punch biopsies taken from the plaque's periphery demonstrated well-differentiated SCC (KA type), as well as a lichenoid inflammatory process, epidermal hyperplasia, and cystic and endophytic squamous proliferation suggestive of hypertrophic lichen planus (HLP).

In consideration of the size and number of the lesions as well as the prolonged wound healing with prior surgery, the patient consented to treatment with intralesional MTX (1 mL of 12.5 mg/mL every 2 weeks) rather than undergoing further surgery. The MTX injection was distributed between the lesions on the anterior and posterior aspects of the lower right leg. At each injection session, the size, thickness, and nodularity of the tumor decreased with markedly less pruritus and symptomatic relief was achieved. After 3 injection sessions, resulting in a total of 3 mL of 12.5 mg/mL of MTX, biopsies were taken from the residual atrophic scar on the anterior aspect of the right leg and the remaining 3 papules on the posterior aspect of the right leg to rule out HLP and invasive SCC. The pathology report commented on the presence of prurigo nodules without any evidence of SCC.

At 3-month follow-up, the patient demonstrated no new lesions or recurrence (Figure, C and D). The right leg continued to heal with scarring and postinflammatory pigmentary changes. The patient was monitored for recurrence and to determine the diagnosis of HLP.

Comment

We report the development of multiple KAs arising both from within surgical margins and de novo, and resolution with intralesional MTX. Keratoacanthomas, especially various KA types, have been observed to develop due to various types of trauma, including sites of surgical scars, lichen planus, tattoos, thermal burns, radiation, and discoid lupus erythematosus, and within skin grafts and donor sites.^5-19

Hypertrophic lichen planus is a chronic variant of lichen planus that often is found on the pretibial areas of the lower legs.¹³ Both SCC and reactive KAs have been observed to develop within lesions of HLP.¹⁴ Our pathologist commented on the presence of a lichenoid infiltrate with necrotic keratinocytes and epidermal hyperplasia suspicious for HLP, with a small focus of cystic and endophytic squamous proliferation. The latter lacked notable atypia or an invasive component and could represent an irritated infundibular cyst versus an early evolving KA.

The lichenoid inflammation is suspicious for HLP, which has been associated with eruptive KAs^13-16 and may have contributed to the development of persistent KAs in our patient, both in sites of surgical scars (the anterior aspect of the leg) and in uninvolved skin (the posterior aspect of the leg). Trauma from the prior surgery may have stimulated a local inflammatory response and, if coupled with a preexisting underlying chronic inflammatory condition such as HLP, may have triggered the development of new lesions on the posterior leg. Skin pathergy reactions also are caused by an upregulated inflammatory response, which is reduced with immunosuppressive agents such as MTX.¹²

In our patient, there was both an isotopic and isomorphic response. The term isotopic response refers to the occurrence of a new skin disorder at the site of another unrelated and already healed skin disease. It was first defined by Wolf and Wolf²⁰ in 1985 and hence is also known as Wolf isotopic response. The isotopic response in our patient occurred in the setting of lichen planus. The isomorphic response indicates the appearance of typical skin lesions of an existing dermatosis at sites of other skin injuries.

Initially, we thought the patient had recurrence of SCC, but with the rapid development of multiple lesions, the diagnosis of multiple KAs was more likely. Kimyai-Asadi et al⁸ demonstrated that surgical trauma can precede the development of KAs, as they reported a patient who developed a KA at an excision site. Tamir et al⁷ reported the simultaneous appearance of KAs in burn scars and skin graft donor sites 4 months after a 40% total body surface area burn. Hamilton et al¹¹ described surgical trauma from a split-skin graft donor site as a trigger for the onset of a KA.

Multiple treatment alternatives exist for KAs, with the standard of care for large or high-risk KAs being excisional surgery^21,22; however, other approaches may need to be considered in certain cases, such as with multiple KAs in which lesions may be large and extensive, thereby yielding poor cosmetic outcomes, or with increased surgical risk.²³ Furthermore, multiple KAs that develop in the setting of surgical scars require special consideration. Topical 5-fluorouracil, various systemic and intralesional agents (eg, retinoids, interferon, bleomycin, MTX), laser therapy, electrodesiccation and curettage, radiotherapy, and photodynamic therapy all have been reported as methods employed for the treatment of KA.^23-27 Goldberg et al⁵ reported cases of resolution of eruptive KAs arising in both surgical and nonsurgical sites with a combination of deep shave excision, MMS, curettage and desiccation, and oral isotretinoin.

For our patient, we opted for treatment with intralesional MTX, both due to its effectiveness for solitary KAs and reasonably decreased risk of morbidity compared to surgical excision of regions of the pretibial calves. Treatment with MTX would not have been attempted if there was any clinical doubt that the lesions were not the well-differentiated KA type. Also, we had a low threshold for discontinuing therapy and reverting to MMS treatment if any of the lesions displayed a paradoxical growth post-MTX treatment or failed to respond after 3 treatments. Intralesional MTX is less invasive, relatively inexpensive, and a treatment modality with decreased morbidity for KAs, especially for multiple KAs. It should be considered as a potential alternative to surgery in such cases.^23-27

Malignant melanoma has continually shown a pattern of increased incidence and mortality over the last 50 years, especially in fair-skinned individuals. In fact, malignant melanoma has the highest mortality rate of all skin cancers in white individuals. Currently, wide local surgical excision is the mainstay of treatment of primary cutaneous melanomas.¹ The margins vary in size according to the Breslow thickness (or depth) of the involved tumor. As such, advancements in melanoma treatment continue to be studied. We present the case of a patient with invasive melanoma that was cleared with topical imiquimod.

Case Report

A 71-year-old man presented with biopsy-proven malignant melanoma on the right posterior scalp that was diagnosed a few weeks prior. The melanoma was invasive with a depth of 0.73 mm. The patient also had an approximately 8-cm, irregular, patchy area of hyperpigmentation involving almost the entire crown of the head (Figure 1A). The biopsy site used for melanoma diagnosis was on the right posterior aspect of the hyperpigmented area where a symptomatic pigmented papule was located. To determine if the rest of this macule represented an extension of the proven malignancy, surveillance biopsies were taken at the 12 o'clock (anterior aspect), 3 o'clock, 6 o'clock, and 9 o'clock positions on the head. All of the biopsies came back as lentigo simplex, which presented a clinical problem in that the boundaries of the invasive melanoma merged with the lentigo simplex and were not clinically apparent. Because an exact boundary could not be visualized, the entire area was treated with imiquimod cream 5% once nightly at bedtime for 4 weeks prior to excision of the original biopsy site. There was a notable decrease in hyperpigmentation in the treated area after 4 weeks of therapy (Figure 1B). The original biopsy site was then excised with a 0.6-cm margin and a complex linear repair was performed. Histologic examination of the excised specimen showed no residual melanoma.

Comment

Although surgical excision is the recommended treatment of cutaneous melanoma,¹ in some cases the defect following an excision can be quite large or even disfiguring. To minimize the size of the excision site, other treatment modalities should be studied. Imiquimod is an immunomodulating agent that exerts antitumor and antiviral effects. The US Food and Drug Administration has approved imiquimod for treatment of genital warts, actinic keratoses, and superficial basal cell carcinoma.² The most common side effects of topical imiquimod involve application-site reactions such as erythema, swelling, and crusting of the treated area. Ulceration of the skin also is possible. A small percentage of individuals have experienced systemic flulike symptoms after using topical imiquimod. Topical imiquimod has been used off label to treat noninvasive forms of melanoma. The topical therapy has been reported to clear melanoma in situ and lentigo maligna.^2,3 In addition, imiquimod has been used as a palliative therapy for cutaneous metastatic melanoma.^4,5 In another case of a primary melanoma that responded to topical imiquimod, clinical and histological clearance of a recurrent oral mucosa melanoma was obtained.⁶

Moon and Spencer⁷ reported a case of an invasive melanoma that was cleared with topical imiquimod. A 93-year-old woman presented with a central 2.75-mm thick invasive melanoma surrounded by a large area of melanoma in situ involving the left cheek and eyelid. The excised tissue was stained for CD31 and D2-40 to rule out intravascular and intralymphatic spread (Figure 2A). The standard-of-care treatment for this case would involve surgical excision with 2-cm margins and a sentinel lymph node biopsy, but given the morbidity involved with the surgery, an alternative treatment plan was made with the patient. The patient completed 5 weeks of topical imiquimod therapy and then underwent wide local excision with a 1-cm margin. Extensive histological examination of the excised specimen showed no residual melanoma; in fact, there was a near absence of junctional melanocytes that would normally have been seen. The specimen underwent immunoperoxidase staining for Melan-A (Figure 2B). The patient was followed for 14 months with no evidence of recurrence.⁷

Conclusion

We describe a patient who achieved complete histologic clearance of invasive melanoma following treatment with topical imiquimod. Four weeks of topical therapy completely cleared an invasive melanoma that was 0.73-mm thick. Follow-up was recommended for the patient because long-term outcomes of this therapy are unknown. More studies demonstrating reliability and reproducibility are needed to evaluate the role of topical imiquimod in melanoma treatment; however, our case shows the potential of this topical modality.

Malignant melanoma has continually shown a pattern of increased incidence and mortality over the last 50 years, especially in fair-skinned individuals. In fact, malignant melanoma has the highest mortality rate of all skin cancers in white individuals. Currently, wide local surgical excision is the mainstay of treatment of primary cutaneous melanomas.¹ The margins vary in size according to the Breslow thickness (or depth) of the involved tumor. As such, advancements in melanoma treatment continue to be studied. We present the case of a patient with invasive melanoma that was cleared with topical imiquimod.

Case Report

A 71-year-old man presented with biopsy-proven malignant melanoma on the right posterior scalp that was diagnosed a few weeks prior. The melanoma was invasive with a depth of 0.73 mm. The patient also had an approximately 8-cm, irregular, patchy area of hyperpigmentation involving almost the entire crown of the head (Figure 1A). The biopsy site used for melanoma diagnosis was on the right posterior aspect of the hyperpigmented area where a symptomatic pigmented papule was located. To determine if the rest of this macule represented an extension of the proven malignancy, surveillance biopsies were taken at the 12 o'clock (anterior aspect), 3 o'clock, 6 o'clock, and 9 o'clock positions on the head. All of the biopsies came back as lentigo simplex, which presented a clinical problem in that the boundaries of the invasive melanoma merged with the lentigo simplex and were not clinically apparent. Because an exact boundary could not be visualized, the entire area was treated with imiquimod cream 5% once nightly at bedtime for 4 weeks prior to excision of the original biopsy site. There was a notable decrease in hyperpigmentation in the treated area after 4 weeks of therapy (Figure 1B). The original biopsy site was then excised with a 0.6-cm margin and a complex linear repair was performed. Histologic examination of the excised specimen showed no residual melanoma.

Comment

Although surgical excision is the recommended treatment of cutaneous melanoma,¹ in some cases the defect following an excision can be quite large or even disfiguring. To minimize the size of the excision site, other treatment modalities should be studied. Imiquimod is an immunomodulating agent that exerts antitumor and antiviral effects. The US Food and Drug Administration has approved imiquimod for treatment of genital warts, actinic keratoses, and superficial basal cell carcinoma.² The most common side effects of topical imiquimod involve application-site reactions such as erythema, swelling, and crusting of the treated area. Ulceration of the skin also is possible. A small percentage of individuals have experienced systemic flulike symptoms after using topical imiquimod. Topical imiquimod has been used off label to treat noninvasive forms of melanoma. The topical therapy has been reported to clear melanoma in situ and lentigo maligna.^2,3 In addition, imiquimod has been used as a palliative therapy for cutaneous metastatic melanoma.^4,5 In another case of a primary melanoma that responded to topical imiquimod, clinical and histological clearance of a recurrent oral mucosa melanoma was obtained.⁶

Moon and Spencer⁷ reported a case of an invasive melanoma that was cleared with topical imiquimod. A 93-year-old woman presented with a central 2.75-mm thick invasive melanoma surrounded by a large area of melanoma in situ involving the left cheek and eyelid. The excised tissue was stained for CD31 and D2-40 to rule out intravascular and intralymphatic spread (Figure 2A). The standard-of-care treatment for this case would involve surgical excision with 2-cm margins and a sentinel lymph node biopsy, but given the morbidity involved with the surgery, an alternative treatment plan was made with the patient. The patient completed 5 weeks of topical imiquimod therapy and then underwent wide local excision with a 1-cm margin. Extensive histological examination of the excised specimen showed no residual melanoma; in fact, there was a near absence of junctional melanocytes that would normally have been seen. The specimen underwent immunoperoxidase staining for Melan-A (Figure 2B). The patient was followed for 14 months with no evidence of recurrence.⁷

Conclusion

We describe a patient who achieved complete histologic clearance of invasive melanoma following treatment with topical imiquimod. Four weeks of topical therapy completely cleared an invasive melanoma that was 0.73-mm thick. Follow-up was recommended for the patient because long-term outcomes of this therapy are unknown. More studies demonstrating reliability and reproducibility are needed to evaluate the role of topical imiquimod in melanoma treatment; however, our case shows the potential of this topical modality.

Malignant melanoma has continually shown a pattern of increased incidence and mortality over the last 50 years, especially in fair-skinned individuals. In fact, malignant melanoma has the highest mortality rate of all skin cancers in white individuals. Currently, wide local surgical excision is the mainstay of treatment of primary cutaneous melanomas.¹ The margins vary in size according to the Breslow thickness (or depth) of the involved tumor. As such, advancements in melanoma treatment continue to be studied. We present the case of a patient with invasive melanoma that was cleared with topical imiquimod.

Case Report

A 71-year-old man presented with biopsy-proven malignant melanoma on the right posterior scalp that was diagnosed a few weeks prior. The melanoma was invasive with a depth of 0.73 mm. The patient also had an approximately 8-cm, irregular, patchy area of hyperpigmentation involving almost the entire crown of the head (Figure 1A). The biopsy site used for melanoma diagnosis was on the right posterior aspect of the hyperpigmented area where a symptomatic pigmented papule was located. To determine if the rest of this macule represented an extension of the proven malignancy, surveillance biopsies were taken at the 12 o'clock (anterior aspect), 3 o'clock, 6 o'clock, and 9 o'clock positions on the head. All of the biopsies came back as lentigo simplex, which presented a clinical problem in that the boundaries of the invasive melanoma merged with the lentigo simplex and were not clinically apparent. Because an exact boundary could not be visualized, the entire area was treated with imiquimod cream 5% once nightly at bedtime for 4 weeks prior to excision of the original biopsy site. There was a notable decrease in hyperpigmentation in the treated area after 4 weeks of therapy (Figure 1B). The original biopsy site was then excised with a 0.6-cm margin and a complex linear repair was performed. Histologic examination of the excised specimen showed no residual melanoma.

Comment

Although surgical excision is the recommended treatment of cutaneous melanoma,¹ in some cases the defect following an excision can be quite large or even disfiguring. To minimize the size of the excision site, other treatment modalities should be studied. Imiquimod is an immunomodulating agent that exerts antitumor and antiviral effects. The US Food and Drug Administration has approved imiquimod for treatment of genital warts, actinic keratoses, and superficial basal cell carcinoma.² The most common side effects of topical imiquimod involve application-site reactions such as erythema, swelling, and crusting of the treated area. Ulceration of the skin also is possible. A small percentage of individuals have experienced systemic flulike symptoms after using topical imiquimod. Topical imiquimod has been used off label to treat noninvasive forms of melanoma. The topical therapy has been reported to clear melanoma in situ and lentigo maligna.^2,3 In addition, imiquimod has been used as a palliative therapy for cutaneous metastatic melanoma.^4,5 In another case of a primary melanoma that responded to topical imiquimod, clinical and histological clearance of a recurrent oral mucosa melanoma was obtained.⁶

Moon and Spencer⁷ reported a case of an invasive melanoma that was cleared with topical imiquimod. A 93-year-old woman presented with a central 2.75-mm thick invasive melanoma surrounded by a large area of melanoma in situ involving the left cheek and eyelid. The excised tissue was stained for CD31 and D2-40 to rule out intravascular and intralymphatic spread (Figure 2A). The standard-of-care treatment for this case would involve surgical excision with 2-cm margins and a sentinel lymph node biopsy, but given the morbidity involved with the surgery, an alternative treatment plan was made with the patient. The patient completed 5 weeks of topical imiquimod therapy and then underwent wide local excision with a 1-cm margin. Extensive histological examination of the excised specimen showed no residual melanoma; in fact, there was a near absence of junctional melanocytes that would normally have been seen. The specimen underwent immunoperoxidase staining for Melan-A (Figure 2B). The patient was followed for 14 months with no evidence of recurrence.⁷

Conclusion

We describe a patient who achieved complete histologic clearance of invasive melanoma following treatment with topical imiquimod. Four weeks of topical therapy completely cleared an invasive melanoma that was 0.73-mm thick. Follow-up was recommended for the patient because long-term outcomes of this therapy are unknown. More studies demonstrating reliability and reproducibility are needed to evaluate the role of topical imiquimod in melanoma treatment; however, our case shows the potential of this topical modality.

Case Report

A 78-year-old man presented for evaluation of 4 painful keratotic nodules that had appeared on the dorsal aspect of the right thumb, the first web space of the right hand, and the first web space of the left hand. The nodules developed in pericicatricial skin following Mohs micrographic surgery to the affected areas for treatment of invasive squamous cell carcinomas (SCCs) 2 months prior. The patient had worked in lawn maintenance for decades and continued to garden on an avocational basis. He denied exposure to angling or aquariums.

On physical examination the lesions appeared as firm, dusky-violaceous, crusted nodules (Figure 1). Brown patches of hyperpigmentation or characteristic cornlike elevations of the palm were not present to implicate arsenic exposure. Extensive sun damage to the face, neck, forearms, and dorsal aspect of the hands was noted. Epitrochlear lymphadenopathy or lymphangitic streaking were not appreciated. Routine hematologic parameters including leukocyte count were normal, except for chronic thrombocytopenia. Computerized tomography of the abdomen demonstrated no hepatosplenomegaly or enlarged lymph nodes. Hematoxylin and eosin staining of biopsy specimens from the right thumb showed irregular squamous epithelial hyperplasia with an impetiginized scale crust and pustular tissue reaction, including suppurative abscess formation in the dermis (Figure 2). Initial acid-fast staining performed on the biopsy from the right thumb was negative for microorganisms. Given the concerning histologic features indicating infection, a tissue culture was performed. Subsequent growth on Lowenstein-Jensen culture medium confirmed infection with Mycobacterium avium complex (MAC). The patient was started on clarithromycin 500 mg twice daily in accordance with laboratory susceptibilities, and the cutaneous nodules improved. Unfortunately, the patient died 6 months later secondary to cardiac arrest.

Comment

The genus Mycobacterium comprises more than 130 described bacteria, including the precipitants of tuberculosis and leprosy. Mycobacterium avium complex--an umbrella term for M avium, Mycobacterium intracellulare, and other close relatives--is a member of the genus that maintains a low pathogenicity for healthy individuals.^1,2 Nonetheless, MAC accounts for more than 70% of cases of nontuberculous mycobacterial disease in the United States.³ Mycobacterium avium complex typically acts as a respiratory pathogen, but infection may manifest with lymphadenitis, osteomyelitis, hepatosplenomegaly, or skin involvement. Disseminated MAC infection can occur in patients with defective immune systems, including those with conditions such as AIDS or hairy cell leukemia and those undergoing immunosuppressive therapy.^1,4 Although uncommon, cutaneous infection with MAC occurs via 3 possible mechanisms: (1) primary inoculation, (2) lymphogenous extension, or (3) hematologic dissemination.⁴ According to a PubMed search of articles indexed for MEDLINE using the terms primary cutaneous Mycobacterium avium complex and MAC skin infection, only 11 known cases of primary cutaneous MAC infection have been reported in the English-language literature,^4-14  the most recent being a report by Landriscina et al.¹¹

A Runyon group III bacillus, MAC is a slow-growing nonchromogen that is ubiquitous in nature.¹⁵ It has been isolated from soil, water, house dust, vegetables, eggs, and milk. According to Reed et al,³ occupational exposure to soil is an independent risk factor for MAC infection, with individuals reporting more than 6 years of cumulative participation in lawn and landscaping services, farming, or other occupations involving substantial exposure to dirt or dust most likely to be MAC-positive. Cutaneous MAC infection may be associated with water exposure, as Sugita et al² described one familial outbreak of cutaneous MAC infection linked to use of a circulating, constantly heated bathwater system. With respect to US geography, individuals living in rural areas of the South seem most prone to MAC infection.³

Primary cutaneous infection with MAC occurs after a breach in the skin surface, though this fact may not be elicited by history. Modes of entry include minor abrasions after falling,¹ small wounds,² traumatic inoculation,¹⁵ and intramuscular injection.¹⁶ Clinically, cutaneous lesions of MAC are protean. In the literature, clinical presentation is described as a polymorphous appearance with scaling plaques, verrucous nodules, crusted ulcers, inflammatory nodules, dermatitis, panniculitis, draining sinuses, ecthymatous lesions, sporotrichoid growth patterns, or rosacealike papulopustules.^1,15,17 Lesions may affect the arms and legs, trunk, buttocks, and face.¹⁸

The differential diagnosis of MAC infection includes lupus vulgaris, Mycobacterium marinum infection (also known as swimming pool granuloma), sporotrichosis, nocardiosis, sarcoidosis, neutrophilic dermatosis, pyoderma gangrenosum, and cutaneous blastomycosis. Given its rarity and variability, diagnosis of MAC infection requires a high index of suspicion. Cutaneous MAC infection should be considered if a nodule, plaque, or ulcer fails to respond to conventional treatment, especially in patients with a history of environmental exposure and possible injury to the skin.

We report a rare case of primary cutaneous MAC infection arising in SCC excision sites in a patient without known immune deficiency. This presentation may have occurred for several reasons. First, the surgical excision sites coupled with the substantial occupational and recreational exposure to soil experienced by our patient may have served as portals for infection. Although SCCs are common on the hands, Mohs micrographic surgery is not always performed for excision; in our patient's case, this approach allowed for maximum tissue conservation and preserved manual function given the number and location of the lesions. Second, despite an overtly intact immune system, our patient may have harbored an occult immune deficiency, predisposing him to dermatologic infection with a microorganism of low intrinsic virulence and recurrent malignant neoplasms. This presentation may have been the first clinical indication of subtle immune compromise. For example, inadequate proinflammatory cytokines may contribute to both mycobacterial and malignant disease. A potential risk of inhibition of tumor necrosis factor α is the unmasking of tuberculosis or lymphoma.^19,20 Likewise, IFN-γ is vital in suppressing mycobacteria and malignancy. Yonekura et al²¹ found that IFN-γ induces apoptosis in oral SCC lines. It follows that a paucity of IFN-γ could allow neoplastic growth. Normal function of IFN-γ prompts microbicidal activity in macrophages and stimulates granuloma formation, both of which combat mycobacterial infection.¹⁹ A final postulation is that a simmering cutaneous MAC infection precipitated neoplastic degeneration into SCC, much the same way that the human papillomavirus has been correlated in the carcinogenesis of cervical cancer. As an intracellular microbe, MAC could cause the genetic machinery of skin cells to go awry. Kullavanijaya et al¹⁸ described a patient with cutaneous MAC in association with cervical cancer.

Conclusion

This association of primary cutaneous MAC infection and cutaneous malignancy in a reportedly immunocompetent patient is rare. Cancer patients, as noted by Feld et al,²² are 3 times more likely to develop infections with mycobacteria, with SCC, lymphoma, and leukemia being most commonly indicated. A specific immune deficit in the IFN-γ receptor is known to confer a selective predisposition to mycobacterial infection.^23,24 Toyoda et al²⁵ outlined the case of a pediatric patient with IFN-γ receptor 2 deficiency who presented with disseminated MAC infection and later succumbed to multiple SCCs of the hands and face. The authors' assertion was that inherited disorders of IFN-γ-mediated immunity may be associated with SCCs.²⁵ Unfortunately, our patient died before more specific immunological testing could be conducted. This case highlights the remarkable singularity of primary cutaneous MAC infection in association with multiple SCCs with seemingly intact immune status and offers some intriguing hypotheses regarding its occurrence.

Case Report

A 78-year-old man presented for evaluation of 4 painful keratotic nodules that had appeared on the dorsal aspect of the right thumb, the first web space of the right hand, and the first web space of the left hand. The nodules developed in pericicatricial skin following Mohs micrographic surgery to the affected areas for treatment of invasive squamous cell carcinomas (SCCs) 2 months prior. The patient had worked in lawn maintenance for decades and continued to garden on an avocational basis. He denied exposure to angling or aquariums.

On physical examination the lesions appeared as firm, dusky-violaceous, crusted nodules (Figure 1). Brown patches of hyperpigmentation or characteristic cornlike elevations of the palm were not present to implicate arsenic exposure. Extensive sun damage to the face, neck, forearms, and dorsal aspect of the hands was noted. Epitrochlear lymphadenopathy or lymphangitic streaking were not appreciated. Routine hematologic parameters including leukocyte count were normal, except for chronic thrombocytopenia. Computerized tomography of the abdomen demonstrated no hepatosplenomegaly or enlarged lymph nodes. Hematoxylin and eosin staining of biopsy specimens from the right thumb showed irregular squamous epithelial hyperplasia with an impetiginized scale crust and pustular tissue reaction, including suppurative abscess formation in the dermis (Figure 2). Initial acid-fast staining performed on the biopsy from the right thumb was negative for microorganisms. Given the concerning histologic features indicating infection, a tissue culture was performed. Subsequent growth on Lowenstein-Jensen culture medium confirmed infection with Mycobacterium avium complex (MAC). The patient was started on clarithromycin 500 mg twice daily in accordance with laboratory susceptibilities, and the cutaneous nodules improved. Unfortunately, the patient died 6 months later secondary to cardiac arrest.

Comment

The genus Mycobacterium comprises more than 130 described bacteria, including the precipitants of tuberculosis and leprosy. Mycobacterium avium complex--an umbrella term for M avium, Mycobacterium intracellulare, and other close relatives--is a member of the genus that maintains a low pathogenicity for healthy individuals.^1,2 Nonetheless, MAC accounts for more than 70% of cases of nontuberculous mycobacterial disease in the United States.³ Mycobacterium avium complex typically acts as a respiratory pathogen, but infection may manifest with lymphadenitis, osteomyelitis, hepatosplenomegaly, or skin involvement. Disseminated MAC infection can occur in patients with defective immune systems, including those with conditions such as AIDS or hairy cell leukemia and those undergoing immunosuppressive therapy.^1,4 Although uncommon, cutaneous infection with MAC occurs via 3 possible mechanisms: (1) primary inoculation, (2) lymphogenous extension, or (3) hematologic dissemination.⁴ According to a PubMed search of articles indexed for MEDLINE using the terms primary cutaneous Mycobacterium avium complex and MAC skin infection, only 11 known cases of primary cutaneous MAC infection have been reported in the English-language literature,^4-14  the most recent being a report by Landriscina et al.¹¹

A Runyon group III bacillus, MAC is a slow-growing nonchromogen that is ubiquitous in nature.¹⁵ It has been isolated from soil, water, house dust, vegetables, eggs, and milk. According to Reed et al,³ occupational exposure to soil is an independent risk factor for MAC infection, with individuals reporting more than 6 years of cumulative participation in lawn and landscaping services, farming, or other occupations involving substantial exposure to dirt or dust most likely to be MAC-positive. Cutaneous MAC infection may be associated with water exposure, as Sugita et al² described one familial outbreak of cutaneous MAC infection linked to use of a circulating, constantly heated bathwater system. With respect to US geography, individuals living in rural areas of the South seem most prone to MAC infection.³

Primary cutaneous infection with MAC occurs after a breach in the skin surface, though this fact may not be elicited by history. Modes of entry include minor abrasions after falling,¹ small wounds,² traumatic inoculation,¹⁵ and intramuscular injection.¹⁶ Clinically, cutaneous lesions of MAC are protean. In the literature, clinical presentation is described as a polymorphous appearance with scaling plaques, verrucous nodules, crusted ulcers, inflammatory nodules, dermatitis, panniculitis, draining sinuses, ecthymatous lesions, sporotrichoid growth patterns, or rosacealike papulopustules.^1,15,17 Lesions may affect the arms and legs, trunk, buttocks, and face.¹⁸

The differential diagnosis of MAC infection includes lupus vulgaris, Mycobacterium marinum infection (also known as swimming pool granuloma), sporotrichosis, nocardiosis, sarcoidosis, neutrophilic dermatosis, pyoderma gangrenosum, and cutaneous blastomycosis. Given its rarity and variability, diagnosis of MAC infection requires a high index of suspicion. Cutaneous MAC infection should be considered if a nodule, plaque, or ulcer fails to respond to conventional treatment, especially in patients with a history of environmental exposure and possible injury to the skin.

We report a rare case of primary cutaneous MAC infection arising in SCC excision sites in a patient without known immune deficiency. This presentation may have occurred for several reasons. First, the surgical excision sites coupled with the substantial occupational and recreational exposure to soil experienced by our patient may have served as portals for infection. Although SCCs are common on the hands, Mohs micrographic surgery is not always performed for excision; in our patient's case, this approach allowed for maximum tissue conservation and preserved manual function given the number and location of the lesions. Second, despite an overtly intact immune system, our patient may have harbored an occult immune deficiency, predisposing him to dermatologic infection with a microorganism of low intrinsic virulence and recurrent malignant neoplasms. This presentation may have been the first clinical indication of subtle immune compromise. For example, inadequate proinflammatory cytokines may contribute to both mycobacterial and malignant disease. A potential risk of inhibition of tumor necrosis factor α is the unmasking of tuberculosis or lymphoma.^19,20 Likewise, IFN-γ is vital in suppressing mycobacteria and malignancy. Yonekura et al²¹ found that IFN-γ induces apoptosis in oral SCC lines. It follows that a paucity of IFN-γ could allow neoplastic growth. Normal function of IFN-γ prompts microbicidal activity in macrophages and stimulates granuloma formation, both of which combat mycobacterial infection.¹⁹ A final postulation is that a simmering cutaneous MAC infection precipitated neoplastic degeneration into SCC, much the same way that the human papillomavirus has been correlated in the carcinogenesis of cervical cancer. As an intracellular microbe, MAC could cause the genetic machinery of skin cells to go awry. Kullavanijaya et al¹⁸ described a patient with cutaneous MAC in association with cervical cancer.

Conclusion

This association of primary cutaneous MAC infection and cutaneous malignancy in a reportedly immunocompetent patient is rare. Cancer patients, as noted by Feld et al,²² are 3 times more likely to develop infections with mycobacteria, with SCC, lymphoma, and leukemia being most commonly indicated. A specific immune deficit in the IFN-γ receptor is known to confer a selective predisposition to mycobacterial infection.^23,24 Toyoda et al²⁵ outlined the case of a pediatric patient with IFN-γ receptor 2 deficiency who presented with disseminated MAC infection and later succumbed to multiple SCCs of the hands and face. The authors' assertion was that inherited disorders of IFN-γ-mediated immunity may be associated with SCCs.²⁵ Unfortunately, our patient died before more specific immunological testing could be conducted. This case highlights the remarkable singularity of primary cutaneous MAC infection in association with multiple SCCs with seemingly intact immune status and offers some intriguing hypotheses regarding its occurrence.

Case Report

A 78-year-old man presented for evaluation of 4 painful keratotic nodules that had appeared on the dorsal aspect of the right thumb, the first web space of the right hand, and the first web space of the left hand. The nodules developed in pericicatricial skin following Mohs micrographic surgery to the affected areas for treatment of invasive squamous cell carcinomas (SCCs) 2 months prior. The patient had worked in lawn maintenance for decades and continued to garden on an avocational basis. He denied exposure to angling or aquariums.

On physical examination the lesions appeared as firm, dusky-violaceous, crusted nodules (Figure 1). Brown patches of hyperpigmentation or characteristic cornlike elevations of the palm were not present to implicate arsenic exposure. Extensive sun damage to the face, neck, forearms, and dorsal aspect of the hands was noted. Epitrochlear lymphadenopathy or lymphangitic streaking were not appreciated. Routine hematologic parameters including leukocyte count were normal, except for chronic thrombocytopenia. Computerized tomography of the abdomen demonstrated no hepatosplenomegaly or enlarged lymph nodes. Hematoxylin and eosin staining of biopsy specimens from the right thumb showed irregular squamous epithelial hyperplasia with an impetiginized scale crust and pustular tissue reaction, including suppurative abscess formation in the dermis (Figure 2). Initial acid-fast staining performed on the biopsy from the right thumb was negative for microorganisms. Given the concerning histologic features indicating infection, a tissue culture was performed. Subsequent growth on Lowenstein-Jensen culture medium confirmed infection with Mycobacterium avium complex (MAC). The patient was started on clarithromycin 500 mg twice daily in accordance with laboratory susceptibilities, and the cutaneous nodules improved. Unfortunately, the patient died 6 months later secondary to cardiac arrest.

Comment

The genus Mycobacterium comprises more than 130 described bacteria, including the precipitants of tuberculosis and leprosy. Mycobacterium avium complex--an umbrella term for M avium, Mycobacterium intracellulare, and other close relatives--is a member of the genus that maintains a low pathogenicity for healthy individuals.^1,2 Nonetheless, MAC accounts for more than 70% of cases of nontuberculous mycobacterial disease in the United States.³ Mycobacterium avium complex typically acts as a respiratory pathogen, but infection may manifest with lymphadenitis, osteomyelitis, hepatosplenomegaly, or skin involvement. Disseminated MAC infection can occur in patients with defective immune systems, including those with conditions such as AIDS or hairy cell leukemia and those undergoing immunosuppressive therapy.^1,4 Although uncommon, cutaneous infection with MAC occurs via 3 possible mechanisms: (1) primary inoculation, (2) lymphogenous extension, or (3) hematologic dissemination.⁴ According to a PubMed search of articles indexed for MEDLINE using the terms primary cutaneous Mycobacterium avium complex and MAC skin infection, only 11 known cases of primary cutaneous MAC infection have been reported in the English-language literature,^4-14  the most recent being a report by Landriscina et al.¹¹

A Runyon group III bacillus, MAC is a slow-growing nonchromogen that is ubiquitous in nature.¹⁵ It has been isolated from soil, water, house dust, vegetables, eggs, and milk. According to Reed et al,³ occupational exposure to soil is an independent risk factor for MAC infection, with individuals reporting more than 6 years of cumulative participation in lawn and landscaping services, farming, or other occupations involving substantial exposure to dirt or dust most likely to be MAC-positive. Cutaneous MAC infection may be associated with water exposure, as Sugita et al² described one familial outbreak of cutaneous MAC infection linked to use of a circulating, constantly heated bathwater system. With respect to US geography, individuals living in rural areas of the South seem most prone to MAC infection.³

Primary cutaneous infection with MAC occurs after a breach in the skin surface, though this fact may not be elicited by history. Modes of entry include minor abrasions after falling,¹ small wounds,² traumatic inoculation,¹⁵ and intramuscular injection.¹⁶ Clinically, cutaneous lesions of MAC are protean. In the literature, clinical presentation is described as a polymorphous appearance with scaling plaques, verrucous nodules, crusted ulcers, inflammatory nodules, dermatitis, panniculitis, draining sinuses, ecthymatous lesions, sporotrichoid growth patterns, or rosacealike papulopustules.^1,15,17 Lesions may affect the arms and legs, trunk, buttocks, and face.¹⁸

The differential diagnosis of MAC infection includes lupus vulgaris, Mycobacterium marinum infection (also known as swimming pool granuloma), sporotrichosis, nocardiosis, sarcoidosis, neutrophilic dermatosis, pyoderma gangrenosum, and cutaneous blastomycosis. Given its rarity and variability, diagnosis of MAC infection requires a high index of suspicion. Cutaneous MAC infection should be considered if a nodule, plaque, or ulcer fails to respond to conventional treatment, especially in patients with a history of environmental exposure and possible injury to the skin.

We report a rare case of primary cutaneous MAC infection arising in SCC excision sites in a patient without known immune deficiency. This presentation may have occurred for several reasons. First, the surgical excision sites coupled with the substantial occupational and recreational exposure to soil experienced by our patient may have served as portals for infection. Although SCCs are common on the hands, Mohs micrographic surgery is not always performed for excision; in our patient's case, this approach allowed for maximum tissue conservation and preserved manual function given the number and location of the lesions. Second, despite an overtly intact immune system, our patient may have harbored an occult immune deficiency, predisposing him to dermatologic infection with a microorganism of low intrinsic virulence and recurrent malignant neoplasms. This presentation may have been the first clinical indication of subtle immune compromise. For example, inadequate proinflammatory cytokines may contribute to both mycobacterial and malignant disease. A potential risk of inhibition of tumor necrosis factor α is the unmasking of tuberculosis or lymphoma.^19,20 Likewise, IFN-γ is vital in suppressing mycobacteria and malignancy. Yonekura et al²¹ found that IFN-γ induces apoptosis in oral SCC lines. It follows that a paucity of IFN-γ could allow neoplastic growth. Normal function of IFN-γ prompts microbicidal activity in macrophages and stimulates granuloma formation, both of which combat mycobacterial infection.¹⁹ A final postulation is that a simmering cutaneous MAC infection precipitated neoplastic degeneration into SCC, much the same way that the human papillomavirus has been correlated in the carcinogenesis of cervical cancer. As an intracellular microbe, MAC could cause the genetic machinery of skin cells to go awry. Kullavanijaya et al¹⁸ described a patient with cutaneous MAC in association with cervical cancer.

Conclusion

This association of primary cutaneous MAC infection and cutaneous malignancy in a reportedly immunocompetent patient is rare. Cancer patients, as noted by Feld et al,²² are 3 times more likely to develop infections with mycobacteria, with SCC, lymphoma, and leukemia being most commonly indicated. A specific immune deficit in the IFN-γ receptor is known to confer a selective predisposition to mycobacterial infection.^23,24 Toyoda et al²⁵ outlined the case of a pediatric patient with IFN-γ receptor 2 deficiency who presented with disseminated MAC infection and later succumbed to multiple SCCs of the hands and face. The authors' assertion was that inherited disorders of IFN-γ-mediated immunity may be associated with SCCs.²⁵ Unfortunately, our patient died before more specific immunological testing could be conducted. This case highlights the remarkable singularity of primary cutaneous MAC infection in association with multiple SCCs with seemingly intact immune status and offers some intriguing hypotheses regarding its occurrence.

Dislocation of the knee is a severe injury that usually results from high-energy blunt trauma.¹ Recognition of knee dislocations has increased with expansion of the definition beyond radiographically confirmed loss of tibiofemoral articulation to include injury of multiple knee ligaments with multidirectional joint instability, or the rupture of the anterior and posterior cruciate ligaments (ACL, PCL) when no gross dislocation can be identified² (though knee dislocations without rupture of either ligament have been reported^3,4). Knee dislocations account for 0.02% to 0.2% of orthopedic injuries.⁵ These multiligamentous injuries are rare, but their clinical outcomes are often complicated by arthrofibrosis, pain, and instability, as surgeons contend with the competing interests of long-term joint stability and range of motion (ROM).^6-9

Whereas treatment standards for acute knee dislocations are becoming clearer, treatment of subacute and chronic tibiofemoral dislocations and subluxations is less defined.⁵ Success with articulated external fixation originally across the ankle and elbow inspired interest in its use for the knee.^10-12 Richter and Lobenhoffer¹³ and Simonian and colleagues¹⁴ were the first to report on the postoperative use of a hinged external fixation device to help maintain the reduction of chronic fixed posterior knee dislocations. The literature has even supported nonoperative reduction of small fixed anterior or posterior (sagittal) subluxations with knee bracing alone.^15,16 However, there are no reports on treatment of chronic tibial subluxation in the coronal plane.

We report a case of a hinged-knee external fixator (HEF) used alone to reduce a chronic medial tibia subluxation that presented after initial repair of a knee dislocation sustained in a motor vehicle accident. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 51-year-old healthy woman who was traveling out of state sustained multiple orthopedic injuries in a motor vehicle accident. She had a pelvic fracture, a contralateral femoral shaft fracture, significant multiligamentous damage to the right knee, and a cavitary impaction fracture of the tibial eminence with resultant coronal tibial subluxation. Initial magnetic resonance imaging (MRI) showed the tibia injury likely was the result of varus translation, as the medial femoral condyle impacted the tibial spine, disrupting the ACL (Figures 1A, 1B).

On initial presentation to our clinic 5 weeks after injury, x-rays showed progressive medial subluxation of the tibia in relation to the femur with translation of about a third of the tibial width medially (Figures 2A, 2B).

Discussion

Although knee dislocations with multiligamentous involvement are rare, their outcomes can be poor. Fortunately, the principles of managing these complex injuries in the acute stage are becoming clearer. In a systematic review, Levy and colleagues¹⁸ found that operative treatment of a dislocated knee within 3 weeks after injury, compared with nonoperative or delayed treatment, resulted in improved functional outcomes. Ligament repair and reconstruction yielded similar outcomes, though repair of the posterolateral corner had a comparatively higher rate of failure. For associated lateral injuries, Shelbourne and colleagues¹⁷ advocated en masse repair in which the healing tissue complex is reattached to the tibia nonanatomically, without dissecting individual structures—a technique used in the original repair of our patient’s injuries.

Originally designed for other joints, hinged external fixators are now occasionally used for rehabilitation after traumatic knee injury. Stannard and colleagues⁹ recently confirmed the utility of the HEF as a supplement to ligament reconstruction for recovery from acute knee dislocation.⁹ Compared with postoperative use of a hinged-knee brace, HEF use resulted in fewer failed ligament reconstructions as well as equivalent joint ROM and Lysholm and IKDC scores at final follow-up. This clinical outcome is supported by results of kinematic studies of these hinged devices, which are capable of rigid fixation in all planes except sagittal and can reduce stress on intra-articular and periarticular ligaments when placed on the appropriate flexion-extension axis of the knee.^19,20Unfortunately, the situation is more complicated for subacute or chronic tibial subluxation than for acute subluxation. Maak and colleagues¹⁶ described 3 operative steps that are crucial in obtaining desired outcomes in this setting: complete release of scar tissue, re-creation of knee axis through ACL and PCL reconstruction, and postoperative application of a HEF or knee brace. These recommendations mimic the management course described by Richter and Lobenhoffer¹³ and Simonian and colleagues,¹⁴ who treated chronic fixed posterior tibial subluxations with arthrolysis, ligament reconstruction, and use of HEFs for 6 weeks, supporting postoperative rehabilitation. All cases maintained reduction at follow-up after fixator removal.

It is also possible for small fixed anterior or posterior tibial subluxations to be managed nonoperatively. Strobel and colleagues¹⁵ described a series of 109 patients with fixed posterior subluxations treated at night with posterior tibial support braces. Mean subluxation was reduced from 6.93 mm to 2.58 mm after an average treatment period of 180 days. Although 60% of all subluxations were completely reduced, reductions were significantly more successful for those displaced <10 mm.

Management of subacute or chronic fixed coronal tibial subluxations is yet to be described. In this article, we have reported on acceptable reduction of a subacute medial tibial subluxation with use of a HEF for 6 weeks after arthroscopic débridement of a deformed subacute bucket-handle lateral meniscus tear. Our case report is unique in that it describes use of a HEF alone for the reduction of a subacute tibial subluxation in any plane without the need for more extensive ligament reconstruction.

The injury here was primarily a lateral ligamentous injury. In the nonanatomical repair that was performed, the LCL and the iliotibial band were reattached to the proximal-lateral tibia. Had we started treating this injury from the time of the patient’s accident, then, depending on repair integrity, we might have considered acute augmentation of the anatomical repair of LCL with Larson-type reconstruction of the LCL and the popliteofibular ligament. Alternatively, acute reconstruction of the LCL and popliteus would be considered if the lateral structures were either irreparable or of very poor quality. In addition, had we initially seen the coronal instability/translation, we might have acutely considered either a staged procedure of a multiplanar external fixator or a HEF.

Given the narrowed lateral joint space, the débridement of the lateral meniscus, and the risk of developing posttraumatic arthritis, our patient will probably need total knee arthroplasty (TKA) at some point. We informed her that she had advanced lateral compartment joint space narrowing and arthritic progression and that she would eventually need TKA based on pain or dysfunction. We think the longevity of that TKA will be predictable and good, as she now had improved tibiofemoral alignment and stability of the collateral ligamentous structures. If she had been allowed to maintain the coronally subluxed position, it would have led to medial ligamentous attenuation and would have compromised the success and longevity of the TKA. In essence, a crucial part of the utility of the HEF was improved coronal tibiofemoral alignment and, therefore, decreased abnormal forces on both the repaired lateral ligaments and the native medial ligamentous structures. Although temporary external fixation issues related to infection risk and patient discomfort are recognized,^21-23 use of HEF alone can be part of the treatment considerations for fixed tibial subluxations in any plane when they present after treatment for multiligamentous injury.

Am J Orthop. 2016;45(7):E497-E502. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Dislocation of the knee is a severe injury that usually results from high-energy blunt trauma.¹ Recognition of knee dislocations has increased with expansion of the definition beyond radiographically confirmed loss of tibiofemoral articulation to include injury of multiple knee ligaments with multidirectional joint instability, or the rupture of the anterior and posterior cruciate ligaments (ACL, PCL) when no gross dislocation can be identified² (though knee dislocations without rupture of either ligament have been reported^3,4). Knee dislocations account for 0.02% to 0.2% of orthopedic injuries.⁵ These multiligamentous injuries are rare, but their clinical outcomes are often complicated by arthrofibrosis, pain, and instability, as surgeons contend with the competing interests of long-term joint stability and range of motion (ROM).^6-9

Whereas treatment standards for acute knee dislocations are becoming clearer, treatment of subacute and chronic tibiofemoral dislocations and subluxations is less defined.⁵ Success with articulated external fixation originally across the ankle and elbow inspired interest in its use for the knee.^10-12 Richter and Lobenhoffer¹³ and Simonian and colleagues¹⁴ were the first to report on the postoperative use of a hinged external fixation device to help maintain the reduction of chronic fixed posterior knee dislocations. The literature has even supported nonoperative reduction of small fixed anterior or posterior (sagittal) subluxations with knee bracing alone.^15,16 However, there are no reports on treatment of chronic tibial subluxation in the coronal plane.

We report a case of a hinged-knee external fixator (HEF) used alone to reduce a chronic medial tibia subluxation that presented after initial repair of a knee dislocation sustained in a motor vehicle accident. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 51-year-old healthy woman who was traveling out of state sustained multiple orthopedic injuries in a motor vehicle accident. She had a pelvic fracture, a contralateral femoral shaft fracture, significant multiligamentous damage to the right knee, and a cavitary impaction fracture of the tibial eminence with resultant coronal tibial subluxation. Initial magnetic resonance imaging (MRI) showed the tibia injury likely was the result of varus translation, as the medial femoral condyle impacted the tibial spine, disrupting the ACL (Figures 1A, 1B).

On initial presentation to our clinic 5 weeks after injury, x-rays showed progressive medial subluxation of the tibia in relation to the femur with translation of about a third of the tibial width medially (Figures 2A, 2B).

Discussion

Although knee dislocations with multiligamentous involvement are rare, their outcomes can be poor. Fortunately, the principles of managing these complex injuries in the acute stage are becoming clearer. In a systematic review, Levy and colleagues¹⁸ found that operative treatment of a dislocated knee within 3 weeks after injury, compared with nonoperative or delayed treatment, resulted in improved functional outcomes. Ligament repair and reconstruction yielded similar outcomes, though repair of the posterolateral corner had a comparatively higher rate of failure. For associated lateral injuries, Shelbourne and colleagues¹⁷ advocated en masse repair in which the healing tissue complex is reattached to the tibia nonanatomically, without dissecting individual structures—a technique used in the original repair of our patient’s injuries.

Originally designed for other joints, hinged external fixators are now occasionally used for rehabilitation after traumatic knee injury. Stannard and colleagues⁹ recently confirmed the utility of the HEF as a supplement to ligament reconstruction for recovery from acute knee dislocation.⁹ Compared with postoperative use of a hinged-knee brace, HEF use resulted in fewer failed ligament reconstructions as well as equivalent joint ROM and Lysholm and IKDC scores at final follow-up. This clinical outcome is supported by results of kinematic studies of these hinged devices, which are capable of rigid fixation in all planes except sagittal and can reduce stress on intra-articular and periarticular ligaments when placed on the appropriate flexion-extension axis of the knee.^19,20Unfortunately, the situation is more complicated for subacute or chronic tibial subluxation than for acute subluxation. Maak and colleagues¹⁶ described 3 operative steps that are crucial in obtaining desired outcomes in this setting: complete release of scar tissue, re-creation of knee axis through ACL and PCL reconstruction, and postoperative application of a HEF or knee brace. These recommendations mimic the management course described by Richter and Lobenhoffer¹³ and Simonian and colleagues,¹⁴ who treated chronic fixed posterior tibial subluxations with arthrolysis, ligament reconstruction, and use of HEFs for 6 weeks, supporting postoperative rehabilitation. All cases maintained reduction at follow-up after fixator removal.

It is also possible for small fixed anterior or posterior tibial subluxations to be managed nonoperatively. Strobel and colleagues¹⁵ described a series of 109 patients with fixed posterior subluxations treated at night with posterior tibial support braces. Mean subluxation was reduced from 6.93 mm to 2.58 mm after an average treatment period of 180 days. Although 60% of all subluxations were completely reduced, reductions were significantly more successful for those displaced <10 mm.

Management of subacute or chronic fixed coronal tibial subluxations is yet to be described. In this article, we have reported on acceptable reduction of a subacute medial tibial subluxation with use of a HEF for 6 weeks after arthroscopic débridement of a deformed subacute bucket-handle lateral meniscus tear. Our case report is unique in that it describes use of a HEF alone for the reduction of a subacute tibial subluxation in any plane without the need for more extensive ligament reconstruction.

The injury here was primarily a lateral ligamentous injury. In the nonanatomical repair that was performed, the LCL and the iliotibial band were reattached to the proximal-lateral tibia. Had we started treating this injury from the time of the patient’s accident, then, depending on repair integrity, we might have considered acute augmentation of the anatomical repair of LCL with Larson-type reconstruction of the LCL and the popliteofibular ligament. Alternatively, acute reconstruction of the LCL and popliteus would be considered if the lateral structures were either irreparable or of very poor quality. In addition, had we initially seen the coronal instability/translation, we might have acutely considered either a staged procedure of a multiplanar external fixator or a HEF.

Given the narrowed lateral joint space, the débridement of the lateral meniscus, and the risk of developing posttraumatic arthritis, our patient will probably need total knee arthroplasty (TKA) at some point. We informed her that she had advanced lateral compartment joint space narrowing and arthritic progression and that she would eventually need TKA based on pain or dysfunction. We think the longevity of that TKA will be predictable and good, as she now had improved tibiofemoral alignment and stability of the collateral ligamentous structures. If she had been allowed to maintain the coronally subluxed position, it would have led to medial ligamentous attenuation and would have compromised the success and longevity of the TKA. In essence, a crucial part of the utility of the HEF was improved coronal tibiofemoral alignment and, therefore, decreased abnormal forces on both the repaired lateral ligaments and the native medial ligamentous structures. Although temporary external fixation issues related to infection risk and patient discomfort are recognized,^21-23 use of HEF alone can be part of the treatment considerations for fixed tibial subluxations in any plane when they present after treatment for multiligamentous injury.

Am J Orthop. 2016;45(7):E497-E502. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Dislocation of the knee is a severe injury that usually results from high-energy blunt trauma.¹ Recognition of knee dislocations has increased with expansion of the definition beyond radiographically confirmed loss of tibiofemoral articulation to include injury of multiple knee ligaments with multidirectional joint instability, or the rupture of the anterior and posterior cruciate ligaments (ACL, PCL) when no gross dislocation can be identified² (though knee dislocations without rupture of either ligament have been reported^3,4). Knee dislocations account for 0.02% to 0.2% of orthopedic injuries.⁵ These multiligamentous injuries are rare, but their clinical outcomes are often complicated by arthrofibrosis, pain, and instability, as surgeons contend with the competing interests of long-term joint stability and range of motion (ROM).^6-9

Whereas treatment standards for acute knee dislocations are becoming clearer, treatment of subacute and chronic tibiofemoral dislocations and subluxations is less defined.⁵ Success with articulated external fixation originally across the ankle and elbow inspired interest in its use for the knee.^10-12 Richter and Lobenhoffer¹³ and Simonian and colleagues¹⁴ were the first to report on the postoperative use of a hinged external fixation device to help maintain the reduction of chronic fixed posterior knee dislocations. The literature has even supported nonoperative reduction of small fixed anterior or posterior (sagittal) subluxations with knee bracing alone.^15,16 However, there are no reports on treatment of chronic tibial subluxation in the coronal plane.

We report a case of a hinged-knee external fixator (HEF) used alone to reduce a chronic medial tibia subluxation that presented after initial repair of a knee dislocation sustained in a motor vehicle accident. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 51-year-old healthy woman who was traveling out of state sustained multiple orthopedic injuries in a motor vehicle accident. She had a pelvic fracture, a contralateral femoral shaft fracture, significant multiligamentous damage to the right knee, and a cavitary impaction fracture of the tibial eminence with resultant coronal tibial subluxation. Initial magnetic resonance imaging (MRI) showed the tibia injury likely was the result of varus translation, as the medial femoral condyle impacted the tibial spine, disrupting the ACL (Figures 1A, 1B).

On initial presentation to our clinic 5 weeks after injury, x-rays showed progressive medial subluxation of the tibia in relation to the femur with translation of about a third of the tibial width medially (Figures 2A, 2B).

Discussion

Although knee dislocations with multiligamentous involvement are rare, their outcomes can be poor. Fortunately, the principles of managing these complex injuries in the acute stage are becoming clearer. In a systematic review, Levy and colleagues¹⁸ found that operative treatment of a dislocated knee within 3 weeks after injury, compared with nonoperative or delayed treatment, resulted in improved functional outcomes. Ligament repair and reconstruction yielded similar outcomes, though repair of the posterolateral corner had a comparatively higher rate of failure. For associated lateral injuries, Shelbourne and colleagues¹⁷ advocated en masse repair in which the healing tissue complex is reattached to the tibia nonanatomically, without dissecting individual structures—a technique used in the original repair of our patient’s injuries.

Originally designed for other joints, hinged external fixators are now occasionally used for rehabilitation after traumatic knee injury. Stannard and colleagues⁹ recently confirmed the utility of the HEF as a supplement to ligament reconstruction for recovery from acute knee dislocation.⁹ Compared with postoperative use of a hinged-knee brace, HEF use resulted in fewer failed ligament reconstructions as well as equivalent joint ROM and Lysholm and IKDC scores at final follow-up. This clinical outcome is supported by results of kinematic studies of these hinged devices, which are capable of rigid fixation in all planes except sagittal and can reduce stress on intra-articular and periarticular ligaments when placed on the appropriate flexion-extension axis of the knee.^19,20Unfortunately, the situation is more complicated for subacute or chronic tibial subluxation than for acute subluxation. Maak and colleagues¹⁶ described 3 operative steps that are crucial in obtaining desired outcomes in this setting: complete release of scar tissue, re-creation of knee axis through ACL and PCL reconstruction, and postoperative application of a HEF or knee brace. These recommendations mimic the management course described by Richter and Lobenhoffer¹³ and Simonian and colleagues,¹⁴ who treated chronic fixed posterior tibial subluxations with arthrolysis, ligament reconstruction, and use of HEFs for 6 weeks, supporting postoperative rehabilitation. All cases maintained reduction at follow-up after fixator removal.

It is also possible for small fixed anterior or posterior tibial subluxations to be managed nonoperatively. Strobel and colleagues¹⁵ described a series of 109 patients with fixed posterior subluxations treated at night with posterior tibial support braces. Mean subluxation was reduced from 6.93 mm to 2.58 mm after an average treatment period of 180 days. Although 60% of all subluxations were completely reduced, reductions were significantly more successful for those displaced <10 mm.

Management of subacute or chronic fixed coronal tibial subluxations is yet to be described. In this article, we have reported on acceptable reduction of a subacute medial tibial subluxation with use of a HEF for 6 weeks after arthroscopic débridement of a deformed subacute bucket-handle lateral meniscus tear. Our case report is unique in that it describes use of a HEF alone for the reduction of a subacute tibial subluxation in any plane without the need for more extensive ligament reconstruction.

The injury here was primarily a lateral ligamentous injury. In the nonanatomical repair that was performed, the LCL and the iliotibial band were reattached to the proximal-lateral tibia. Had we started treating this injury from the time of the patient’s accident, then, depending on repair integrity, we might have considered acute augmentation of the anatomical repair of LCL with Larson-type reconstruction of the LCL and the popliteofibular ligament. Alternatively, acute reconstruction of the LCL and popliteus would be considered if the lateral structures were either irreparable or of very poor quality. In addition, had we initially seen the coronal instability/translation, we might have acutely considered either a staged procedure of a multiplanar external fixator or a HEF.

Given the narrowed lateral joint space, the débridement of the lateral meniscus, and the risk of developing posttraumatic arthritis, our patient will probably need total knee arthroplasty (TKA) at some point. We informed her that she had advanced lateral compartment joint space narrowing and arthritic progression and that she would eventually need TKA based on pain or dysfunction. We think the longevity of that TKA will be predictable and good, as she now had improved tibiofemoral alignment and stability of the collateral ligamentous structures. If she had been allowed to maintain the coronally subluxed position, it would have led to medial ligamentous attenuation and would have compromised the success and longevity of the TKA. In essence, a crucial part of the utility of the HEF was improved coronal tibiofemoral alignment and, therefore, decreased abnormal forces on both the repaired lateral ligaments and the native medial ligamentous structures. Although temporary external fixation issues related to infection risk and patient discomfort are recognized,^21-23 use of HEF alone can be part of the treatment considerations for fixed tibial subluxations in any plane when they present after treatment for multiligamentous injury.

Am J Orthop. 2016;45(7):E497-E502. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Fat embolism syndrome (FES) occurs in long-bone fractures and classically presents with the triad of hypoxia, petechia, and altered mental status, or the criteria of Gurd and Wilson.¹ The Lindeque criteria (femur fracture, pH <7.3, increased work of breathing) are also used.^1,2 FES is a potentially fatal complication, with mortality rates ranging from 10% to 36%.^1,3 FES typically occurs within 24 to 72 hours after initial insult, with one study finding an average of 48.5 hours after injury and an incidence of 0.15% to 2.4%.⁴ The overall FES rate is <1% in retrospective reviews and 11% to 29% in prospective studies.⁵ FES may present without one or all of the Gurd and Wilson criteria,⁶ and cerebral fat embolism (CFE) can be even more difficult to diagnose. Patients with CFE typically present with a wide array of postoperative neurologic deficits, commonly in the 24- to 72-hour window in which FES typically occurs. Correct diagnosis and management of CFE require a high index of suspicion and knowledge of the diagnostic work-up. In the postoperative setting, it can be difficult to distinguish CFE-related neurologic deficits from the normal sequelae of anesthesia, pain medications, and other factors.

In this article, we report the case of a 42-year-old woman who developed CFE after reamed intramedullary nail fixation of femoral and tibial shaft fractures. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 42-year-old woman with no past medical history was injured when a horse reared and fell on her. Initial emergent computed tomography (CT) was negative for intracranial hemorrhage, and injury radiographs were obtained (Figures 1A, 1B).

About 9 hours after surgery and 36 hours after injury, the patient was unresponsive. Vital signs, including oxygen saturation, were within normal limits, but she was unable to verbalize. Physical examination revealed symmetric facial musculature but also generalized weakness and diffuse hypertonicity and hyperreflexia. Initial laboratory results, including complete blood cell count, electrolyte panel, and troponin levels, were unremarkable. Naloxone was administered to rule out opioid overdose. An immediate code stroke and neurology consultation was requested. An emergent CT scan of the brain was negative; an urgent magnetic resonance imaging (MRI) scan showed multiple punctate T2/FLAIR (fluid attenuated inversion recovery) hyperintensities with restricted diffusion, predominantly in a parasagittal white matter distribution (Figure 2).

Discussion

Postoperative Acute Mental Status Change

There are many causes of postoperative mental status change after intramedullary nailing. Change may be cardiogenic, infectious, pharmacologic, or neurologic in origin. Age should be considered in the work-up of postoperative mental status change, as common complications differ between older and younger patients, with geriatric patients at particularly high risk for delirium.

Next to be evaluated are vital signs—particularly hypoxia, as isolated tachycardia may simply be a manifestation of pain. The cardiac system is then assessed with EKG and cardiac-specific laboratory tests, including a troponin level test if there is suspicion of myocardial infarction. PE and FES are complications with a higher prevalence in intramedullary nailing, and pulmonary involvement can be ruled out with the CT with PE protocol. Skin examination is important as well, as FES presents with petechial rash in 60% of patients⁸ (rash was absent in our patient’s case). Narcotic overdose is easily ruled out with administration of naloxone. Infection and sepsis can cause mental changes, though more commonly in the elderly and seldom so soon after surgery. Evaluation for infection and sepsis involves urinalysis and culturing of blood, urine, and other bodily fluids. If there is concern about surgical site infection, the postoperative dressing should be immediately removed and the wound examined. Last, neurologic and embolic phenomena can be initially investigated with CT to rule out hemorrhagic stroke. If CT of the brain is negative, MRI should be performed. MRI is the gold standard for diagnosing ischemic stroke and CFE caused by FES.⁹

Prevalence of Fat Embolism Syndrome

Development of intramedullary fat release in patients with long-bone injuries is common. A prospective study found circulating fat globules in 95% of 43 patients with femur fractures.¹⁰ In another study, transesophageal EKG showed cardiac embolism in 62% of patients who had undergone intramedullary nail fixation.¹¹ Despite this high rate, only 0.9% to 2.2% of patients developed symptomatic FES. Risk factors for FES include younger age, multiple fractures, closed fractures, and nonoperative or delayed management of long-bone fractures.² As already mentioned, average time to FES presentation after long-bone fracture is about 48 hours. One study found that FES typically occurs within 24 to 72 hours after initial insult (average, 48.5 hours) and that the incidence of FES is 0.15% in tibia fractures, 0.78% in femur fractures, and 2.4% in multiple long-bone fractures.⁴ The timeline is consistent with the present case—our patient developed symptoms about 36 hours after injury. In addition, other studies have found a higher mortality rate (5%-15%) for patients with bilateral femur fractures than for patients with only one fracture.^7,12,13 Patients with a floating knee injury (ipsilateral tibia and femur fractures) are at higher risk for FES and have higher overall morbidity and mortality rates in comparison with patients with an isolated femur or tibia fracture, though the increased risk has not been quantified.

Review of Case Literature: FES With CFE

Few cases of FES with symptomatic CFE in the setting of long-bone fracture or long-bone surgery have been reported in the literature. There is wide variation in the development of FES with respect to preoperative or postoperative status and mechanism of injury. Duran and colleagues¹⁴ described a 20-year-old man with ipsilateral tibia and femur fractures caused by gunshots. Twenty-four hours after presentation, he developed tonic-clonic seizures and the classic triad of rash, hypoxia, and altered mental status. MRI confirmed CFE secondary to FES. The patient was optimized neurologically before definitive fixation and was discharged with minimal neurologic deficits on POD-27. Chang and colleagues¹⁵ and Yeo and colleagues¹⁶ described CFE in patients who underwent bilateral total knee arthroplasty. Symptoms developed 9 hours and 2 days after surgery, respectively. Both patients had fat emboli in the lungs and brain, underwent intensive care treatment, and recovered from the initial insult. After discharge at 44 days and 2 weeks, respectively, they fully recovered.

Other patients with CFE have had less favorable outcomes. Chen and colleagues⁶ reported the case of a 31-year-old man who sustained closed femur and tibia fractures in an automobile collision and experienced an acute decline in neurologic status 1 hour after arrival in the emergency department. The patient was intubated, CFE was diagnosed on the basis of MRI findings, and the orthopedic injuries were treated with external fixation. After 2 weeks, the patient was discharged with persistent neurologic deficits and the need for long-term tube feeding. Walshe and colleagues¹⁷ reported the case of a 19-year-old woman who sustained multiple long-bone injuries and traumatic brain injury and showed fat emboli on MRI. The patient experienced brain herniation while in the intensive care unit and later was declared brain-dead. According to the literature, it is important to maintain high suspicion for FES and possible CFE in the setting of high-energy fracture but also to be aware that FES may develop even with nondisplaced fracture or with reaming of the intramedullary canal in elective total joint arthroplasty.¹⁸

Pathophysiology of Fat Embolism Syndrome

The pathophysiology of FES and specifically of CFE is not widely understood. Two main theories on the development of FES have been advanced.

The mechanical theory suggests that exposing intramedullary long-bone contents allows fat to mobilize into the bloodstream.¹⁹ This occurs in the setting of long-bone fracture and in canal preparation during joint replacement surgery. More fat extravasates into the venous system after femur fracture than after tibia fracture, which accounts for the higher risk for FES in femoral shaft fractures and the even higher risk in concomitant femur and tibia fractures.⁴ In addition to there being a risk of fat embolism from the fracture itself, placing the patient in traction or reaming the intramedullary canal may exacerbate this effect by increased extravasation of fat from the medullary canal. With extravasation of fatty bone marrow into the venous system, fat emboli are free to travel back to the lungs, where they can cause infarcts within the lung parenchyma.

In the mechanical theory, presence of PFO may allow fat globules to pass into the systemic circulation and cause end-organ emboli. In the event of cerebral emboli, neurologic symptoms may vary widely and may include diffuse encephalopathy and global deficits.²⁰ Dog studies have found a possible mechanism for CFE in the absence of PFO. One such study, which used femoral pressurization to replicate cemented femoral arthroplasty, found that many fat globules had traversed the lungs after release into bone marrow,²¹ supporting the theory that fat droplets can traverse the pulmonary system without sequestration in the lung parenchyma. Riding and colleagues²² reported finding pulmonary arteriovenous shunts, which are thought to allow CFE to occur in the absence of PFO. More studies are needed to determine the prevalence of shunts and their overall contribution to CFE development in patients with long-bone fracture.

The biochemical theory holds that bodily trauma induces the release of free fatty acids (FFAs) from the capillaries into the bloodstream.²³ This stress response is mediated by catecholamines, which activate the adenyl cyclase pathway, which activates lipase, which hydrolyzes stored triglycerides to FFAs and glycerol. The concentration of circulating FFA was increased in 9 of 10 patients in one study.²³ Increased FFAs in the bloodstream can accelerate local and end-organ clotting, leading to thrombocytopenia and endothelial injury. In addition, patients with hypercoagulable diseases are at higher risk for postoperative thromboembolism.²⁴ However, with a negative hypercoagulable work-up and with negative chest helical CT and EKG, which did not demonstrate PFO, the explanation for CFE in our patient may more likely reside with the arteriovenous shunt theory proposed by Riding and colleagues.²²

Diagnosis and Treatment

Proper care of orthopedic patients who potentially have FES/CFE involves prompt diagnosis, immediate symptomatic care, and early coordination with neurology and medical services to rule out other causes of symptoms. Obtaining advanced imaging to rule out other potential causes and to confirm the diagnosis is crucial. The patient in this case report did not exhibit any focal neurologic deficits, but emergent CT of the brain was indicated to rule out a hemorrhagic event. If a stroke secondary to FES is clinically suspected, MRI should be obtained as soon as possible. Multiple studies have found that the “starfield” pattern, which is best seen as multiple punctate hyperintensities on T2 imaging, is the typical radiographic manifestation of CFE.⁹ This applies to patients who are in the 24- to 72-hour window after long-bone fracture or fixation and who fit Gurd and Wilson¹ criteria or Lindeque^1,2criteria, or who exhibit a change in mental status but have a negative CT scan of the brain, as was the case with our patient. Once the diagnosis is made, treatment involves addressing the symptoms (Figure 4).

Fat Embolism Syndrome in Reamed and Unreamed Nailing

Over the past several decades, the number of long bones fixed with intramedullary nails has increased significantly.²⁶ There is debate regarding whether use of reamed intramedullary nails increases the risk of fat emboli relative to use of unreamed nails, but multiple studies have found no significant difference.^26,27 Pulmonary shunting occurs in both reamed and unreamed nailing; neither technique has an advantage in terms of cardiopulmonary complications. In multiple studies, reamed nails have the advantage of improved healing rates.²⁷ A sheep study compared reamed and unreamed femoral nailing.²⁸ After nailing, sheep lungs were examined histologically for the presence of bone marrow fat embolism. The embolism rate was higher with unreamed nailing (10.25%) than with reamed nailing (6.66%). One large study of the adverse effects of reamed and unreamed nailing in 1226 patients with tibial shaft fracture found that those with open fractures had higher rates of a negative event (nonunion, infection, fasciotomy, hardware failure, need for dynamization) after reamed nailing.²⁹ Patients with closed fractures had fewer events after reamed nailing. The authors concluded there is a potential benefit in outcome with reamed intramedullary nailing in patients with closed tibial shaft fractures, but they did not comment on development of FES. In a study of the effect of subject position on intramedullary pressure and fat embolism release, dogs were positioned either supine or lateral for tibial and femoral reaming.³⁰ The authors measured various physiologic parameters, including cardiac output, pulmonary arterial wedge pressure, arterial and venous blood gas, and blood cell counts. There were no statistically significant differences in values between the 2 groups in any variable, indicating that position does not affect FES development in the orthopedic trauma setting.

Conclusion

FES and CFE are potential devastating sequelae of both long-bone fracture and long-bone instrumentation. It is important to recognize these entities in the acute setting and to consider them in the differential diagnosis of a trauma or postoperative patient who experiences sudden onset of altered mental status with or without dyspnea or a petechial rash. If CFE is suspected, early advanced imaging (including urgent MRI) should be obtained with rapid involvement of a multidisciplinary team that can optimize the chance for successful recovery of both neurologic and physical function. The best treatment, early prevention and diagnosis, maximizes care of symptoms. As is evidenced in this case report, rapid diagnosis and treatment often result in recovery from a majority of the symptoms of FES and CFE.

Am J Orthop. 2016;45(7):E515-E521. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Fat embolism syndrome (FES) occurs in long-bone fractures and classically presents with the triad of hypoxia, petechia, and altered mental status, or the criteria of Gurd and Wilson.¹ The Lindeque criteria (femur fracture, pH <7.3, increased work of breathing) are also used.^1,2 FES is a potentially fatal complication, with mortality rates ranging from 10% to 36%.^1,3 FES typically occurs within 24 to 72 hours after initial insult, with one study finding an average of 48.5 hours after injury and an incidence of 0.15% to 2.4%.⁴ The overall FES rate is <1% in retrospective reviews and 11% to 29% in prospective studies.⁵ FES may present without one or all of the Gurd and Wilson criteria,⁶ and cerebral fat embolism (CFE) can be even more difficult to diagnose. Patients with CFE typically present with a wide array of postoperative neurologic deficits, commonly in the 24- to 72-hour window in which FES typically occurs. Correct diagnosis and management of CFE require a high index of suspicion and knowledge of the diagnostic work-up. In the postoperative setting, it can be difficult to distinguish CFE-related neurologic deficits from the normal sequelae of anesthesia, pain medications, and other factors.

In this article, we report the case of a 42-year-old woman who developed CFE after reamed intramedullary nail fixation of femoral and tibial shaft fractures. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 42-year-old woman with no past medical history was injured when a horse reared and fell on her. Initial emergent computed tomography (CT) was negative for intracranial hemorrhage, and injury radiographs were obtained (Figures 1A, 1B).

About 9 hours after surgery and 36 hours after injury, the patient was unresponsive. Vital signs, including oxygen saturation, were within normal limits, but she was unable to verbalize. Physical examination revealed symmetric facial musculature but also generalized weakness and diffuse hypertonicity and hyperreflexia. Initial laboratory results, including complete blood cell count, electrolyte panel, and troponin levels, were unremarkable. Naloxone was administered to rule out opioid overdose. An immediate code stroke and neurology consultation was requested. An emergent CT scan of the brain was negative; an urgent magnetic resonance imaging (MRI) scan showed multiple punctate T2/FLAIR (fluid attenuated inversion recovery) hyperintensities with restricted diffusion, predominantly in a parasagittal white matter distribution (Figure 2).

Discussion

Postoperative Acute Mental Status Change

There are many causes of postoperative mental status change after intramedullary nailing. Change may be cardiogenic, infectious, pharmacologic, or neurologic in origin. Age should be considered in the work-up of postoperative mental status change, as common complications differ between older and younger patients, with geriatric patients at particularly high risk for delirium.

Next to be evaluated are vital signs—particularly hypoxia, as isolated tachycardia may simply be a manifestation of pain. The cardiac system is then assessed with EKG and cardiac-specific laboratory tests, including a troponin level test if there is suspicion of myocardial infarction. PE and FES are complications with a higher prevalence in intramedullary nailing, and pulmonary involvement can be ruled out with the CT with PE protocol. Skin examination is important as well, as FES presents with petechial rash in 60% of patients⁸ (rash was absent in our patient’s case). Narcotic overdose is easily ruled out with administration of naloxone. Infection and sepsis can cause mental changes, though more commonly in the elderly and seldom so soon after surgery. Evaluation for infection and sepsis involves urinalysis and culturing of blood, urine, and other bodily fluids. If there is concern about surgical site infection, the postoperative dressing should be immediately removed and the wound examined. Last, neurologic and embolic phenomena can be initially investigated with CT to rule out hemorrhagic stroke. If CT of the brain is negative, MRI should be performed. MRI is the gold standard for diagnosing ischemic stroke and CFE caused by FES.⁹

Prevalence of Fat Embolism Syndrome

Development of intramedullary fat release in patients with long-bone injuries is common. A prospective study found circulating fat globules in 95% of 43 patients with femur fractures.¹⁰ In another study, transesophageal EKG showed cardiac embolism in 62% of patients who had undergone intramedullary nail fixation.¹¹ Despite this high rate, only 0.9% to 2.2% of patients developed symptomatic FES. Risk factors for FES include younger age, multiple fractures, closed fractures, and nonoperative or delayed management of long-bone fractures.² As already mentioned, average time to FES presentation after long-bone fracture is about 48 hours. One study found that FES typically occurs within 24 to 72 hours after initial insult (average, 48.5 hours) and that the incidence of FES is 0.15% in tibia fractures, 0.78% in femur fractures, and 2.4% in multiple long-bone fractures.⁴ The timeline is consistent with the present case—our patient developed symptoms about 36 hours after injury. In addition, other studies have found a higher mortality rate (5%-15%) for patients with bilateral femur fractures than for patients with only one fracture.^7,12,13 Patients with a floating knee injury (ipsilateral tibia and femur fractures) are at higher risk for FES and have higher overall morbidity and mortality rates in comparison with patients with an isolated femur or tibia fracture, though the increased risk has not been quantified.

Review of Case Literature: FES With CFE

Few cases of FES with symptomatic CFE in the setting of long-bone fracture or long-bone surgery have been reported in the literature. There is wide variation in the development of FES with respect to preoperative or postoperative status and mechanism of injury. Duran and colleagues¹⁴ described a 20-year-old man with ipsilateral tibia and femur fractures caused by gunshots. Twenty-four hours after presentation, he developed tonic-clonic seizures and the classic triad of rash, hypoxia, and altered mental status. MRI confirmed CFE secondary to FES. The patient was optimized neurologically before definitive fixation and was discharged with minimal neurologic deficits on POD-27. Chang and colleagues¹⁵ and Yeo and colleagues¹⁶ described CFE in patients who underwent bilateral total knee arthroplasty. Symptoms developed 9 hours and 2 days after surgery, respectively. Both patients had fat emboli in the lungs and brain, underwent intensive care treatment, and recovered from the initial insult. After discharge at 44 days and 2 weeks, respectively, they fully recovered.

Other patients with CFE have had less favorable outcomes. Chen and colleagues⁶ reported the case of a 31-year-old man who sustained closed femur and tibia fractures in an automobile collision and experienced an acute decline in neurologic status 1 hour after arrival in the emergency department. The patient was intubated, CFE was diagnosed on the basis of MRI findings, and the orthopedic injuries were treated with external fixation. After 2 weeks, the patient was discharged with persistent neurologic deficits and the need for long-term tube feeding. Walshe and colleagues¹⁷ reported the case of a 19-year-old woman who sustained multiple long-bone injuries and traumatic brain injury and showed fat emboli on MRI. The patient experienced brain herniation while in the intensive care unit and later was declared brain-dead. According to the literature, it is important to maintain high suspicion for FES and possible CFE in the setting of high-energy fracture but also to be aware that FES may develop even with nondisplaced fracture or with reaming of the intramedullary canal in elective total joint arthroplasty.¹⁸

Pathophysiology of Fat Embolism Syndrome

The pathophysiology of FES and specifically of CFE is not widely understood. Two main theories on the development of FES have been advanced.

The mechanical theory suggests that exposing intramedullary long-bone contents allows fat to mobilize into the bloodstream.¹⁹ This occurs in the setting of long-bone fracture and in canal preparation during joint replacement surgery. More fat extravasates into the venous system after femur fracture than after tibia fracture, which accounts for the higher risk for FES in femoral shaft fractures and the even higher risk in concomitant femur and tibia fractures.⁴ In addition to there being a risk of fat embolism from the fracture itself, placing the patient in traction or reaming the intramedullary canal may exacerbate this effect by increased extravasation of fat from the medullary canal. With extravasation of fatty bone marrow into the venous system, fat emboli are free to travel back to the lungs, where they can cause infarcts within the lung parenchyma.

In the mechanical theory, presence of PFO may allow fat globules to pass into the systemic circulation and cause end-organ emboli. In the event of cerebral emboli, neurologic symptoms may vary widely and may include diffuse encephalopathy and global deficits.²⁰ Dog studies have found a possible mechanism for CFE in the absence of PFO. One such study, which used femoral pressurization to replicate cemented femoral arthroplasty, found that many fat globules had traversed the lungs after release into bone marrow,²¹ supporting the theory that fat droplets can traverse the pulmonary system without sequestration in the lung parenchyma. Riding and colleagues²² reported finding pulmonary arteriovenous shunts, which are thought to allow CFE to occur in the absence of PFO. More studies are needed to determine the prevalence of shunts and their overall contribution to CFE development in patients with long-bone fracture.

The biochemical theory holds that bodily trauma induces the release of free fatty acids (FFAs) from the capillaries into the bloodstream.²³ This stress response is mediated by catecholamines, which activate the adenyl cyclase pathway, which activates lipase, which hydrolyzes stored triglycerides to FFAs and glycerol. The concentration of circulating FFA was increased in 9 of 10 patients in one study.²³ Increased FFAs in the bloodstream can accelerate local and end-organ clotting, leading to thrombocytopenia and endothelial injury. In addition, patients with hypercoagulable diseases are at higher risk for postoperative thromboembolism.²⁴ However, with a negative hypercoagulable work-up and with negative chest helical CT and EKG, which did not demonstrate PFO, the explanation for CFE in our patient may more likely reside with the arteriovenous shunt theory proposed by Riding and colleagues.²²

Diagnosis and Treatment

Proper care of orthopedic patients who potentially have FES/CFE involves prompt diagnosis, immediate symptomatic care, and early coordination with neurology and medical services to rule out other causes of symptoms. Obtaining advanced imaging to rule out other potential causes and to confirm the diagnosis is crucial. The patient in this case report did not exhibit any focal neurologic deficits, but emergent CT of the brain was indicated to rule out a hemorrhagic event. If a stroke secondary to FES is clinically suspected, MRI should be obtained as soon as possible. Multiple studies have found that the “starfield” pattern, which is best seen as multiple punctate hyperintensities on T2 imaging, is the typical radiographic manifestation of CFE.⁹ This applies to patients who are in the 24- to 72-hour window after long-bone fracture or fixation and who fit Gurd and Wilson¹ criteria or Lindeque^1,2criteria, or who exhibit a change in mental status but have a negative CT scan of the brain, as was the case with our patient. Once the diagnosis is made, treatment involves addressing the symptoms (Figure 4).

Fat Embolism Syndrome in Reamed and Unreamed Nailing

Over the past several decades, the number of long bones fixed with intramedullary nails has increased significantly.²⁶ There is debate regarding whether use of reamed intramedullary nails increases the risk of fat emboli relative to use of unreamed nails, but multiple studies have found no significant difference.^26,27 Pulmonary shunting occurs in both reamed and unreamed nailing; neither technique has an advantage in terms of cardiopulmonary complications. In multiple studies, reamed nails have the advantage of improved healing rates.²⁷ A sheep study compared reamed and unreamed femoral nailing.²⁸ After nailing, sheep lungs were examined histologically for the presence of bone marrow fat embolism. The embolism rate was higher with unreamed nailing (10.25%) than with reamed nailing (6.66%). One large study of the adverse effects of reamed and unreamed nailing in 1226 patients with tibial shaft fracture found that those with open fractures had higher rates of a negative event (nonunion, infection, fasciotomy, hardware failure, need for dynamization) after reamed nailing.²⁹ Patients with closed fractures had fewer events after reamed nailing. The authors concluded there is a potential benefit in outcome with reamed intramedullary nailing in patients with closed tibial shaft fractures, but they did not comment on development of FES. In a study of the effect of subject position on intramedullary pressure and fat embolism release, dogs were positioned either supine or lateral for tibial and femoral reaming.³⁰ The authors measured various physiologic parameters, including cardiac output, pulmonary arterial wedge pressure, arterial and venous blood gas, and blood cell counts. There were no statistically significant differences in values between the 2 groups in any variable, indicating that position does not affect FES development in the orthopedic trauma setting.

Conclusion

FES and CFE are potential devastating sequelae of both long-bone fracture and long-bone instrumentation. It is important to recognize these entities in the acute setting and to consider them in the differential diagnosis of a trauma or postoperative patient who experiences sudden onset of altered mental status with or without dyspnea or a petechial rash. If CFE is suspected, early advanced imaging (including urgent MRI) should be obtained with rapid involvement of a multidisciplinary team that can optimize the chance for successful recovery of both neurologic and physical function. The best treatment, early prevention and diagnosis, maximizes care of symptoms. As is evidenced in this case report, rapid diagnosis and treatment often result in recovery from a majority of the symptoms of FES and CFE.

Am J Orthop. 2016;45(7):E515-E521. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Fat embolism syndrome (FES) occurs in long-bone fractures and classically presents with the triad of hypoxia, petechia, and altered mental status, or the criteria of Gurd and Wilson.¹ The Lindeque criteria (femur fracture, pH <7.3, increased work of breathing) are also used.^1,2 FES is a potentially fatal complication, with mortality rates ranging from 10% to 36%.^1,3 FES typically occurs within 24 to 72 hours after initial insult, with one study finding an average of 48.5 hours after injury and an incidence of 0.15% to 2.4%.⁴ The overall FES rate is <1% in retrospective reviews and 11% to 29% in prospective studies.⁵ FES may present without one or all of the Gurd and Wilson criteria,⁶ and cerebral fat embolism (CFE) can be even more difficult to diagnose. Patients with CFE typically present with a wide array of postoperative neurologic deficits, commonly in the 24- to 72-hour window in which FES typically occurs. Correct diagnosis and management of CFE require a high index of suspicion and knowledge of the diagnostic work-up. In the postoperative setting, it can be difficult to distinguish CFE-related neurologic deficits from the normal sequelae of anesthesia, pain medications, and other factors.

In this article, we report the case of a 42-year-old woman who developed CFE after reamed intramedullary nail fixation of femoral and tibial shaft fractures. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 42-year-old woman with no past medical history was injured when a horse reared and fell on her. Initial emergent computed tomography (CT) was negative for intracranial hemorrhage, and injury radiographs were obtained (Figures 1A, 1B).

About 9 hours after surgery and 36 hours after injury, the patient was unresponsive. Vital signs, including oxygen saturation, were within normal limits, but she was unable to verbalize. Physical examination revealed symmetric facial musculature but also generalized weakness and diffuse hypertonicity and hyperreflexia. Initial laboratory results, including complete blood cell count, electrolyte panel, and troponin levels, were unremarkable. Naloxone was administered to rule out opioid overdose. An immediate code stroke and neurology consultation was requested. An emergent CT scan of the brain was negative; an urgent magnetic resonance imaging (MRI) scan showed multiple punctate T2/FLAIR (fluid attenuated inversion recovery) hyperintensities with restricted diffusion, predominantly in a parasagittal white matter distribution (Figure 2).

Discussion

Postoperative Acute Mental Status Change

There are many causes of postoperative mental status change after intramedullary nailing. Change may be cardiogenic, infectious, pharmacologic, or neurologic in origin. Age should be considered in the work-up of postoperative mental status change, as common complications differ between older and younger patients, with geriatric patients at particularly high risk for delirium.

Next to be evaluated are vital signs—particularly hypoxia, as isolated tachycardia may simply be a manifestation of pain. The cardiac system is then assessed with EKG and cardiac-specific laboratory tests, including a troponin level test if there is suspicion of myocardial infarction. PE and FES are complications with a higher prevalence in intramedullary nailing, and pulmonary involvement can be ruled out with the CT with PE protocol. Skin examination is important as well, as FES presents with petechial rash in 60% of patients⁸ (rash was absent in our patient’s case). Narcotic overdose is easily ruled out with administration of naloxone. Infection and sepsis can cause mental changes, though more commonly in the elderly and seldom so soon after surgery. Evaluation for infection and sepsis involves urinalysis and culturing of blood, urine, and other bodily fluids. If there is concern about surgical site infection, the postoperative dressing should be immediately removed and the wound examined. Last, neurologic and embolic phenomena can be initially investigated with CT to rule out hemorrhagic stroke. If CT of the brain is negative, MRI should be performed. MRI is the gold standard for diagnosing ischemic stroke and CFE caused by FES.⁹

Prevalence of Fat Embolism Syndrome

Development of intramedullary fat release in patients with long-bone injuries is common. A prospective study found circulating fat globules in 95% of 43 patients with femur fractures.¹⁰ In another study, transesophageal EKG showed cardiac embolism in 62% of patients who had undergone intramedullary nail fixation.¹¹ Despite this high rate, only 0.9% to 2.2% of patients developed symptomatic FES. Risk factors for FES include younger age, multiple fractures, closed fractures, and nonoperative or delayed management of long-bone fractures.² As already mentioned, average time to FES presentation after long-bone fracture is about 48 hours. One study found that FES typically occurs within 24 to 72 hours after initial insult (average, 48.5 hours) and that the incidence of FES is 0.15% in tibia fractures, 0.78% in femur fractures, and 2.4% in multiple long-bone fractures.⁴ The timeline is consistent with the present case—our patient developed symptoms about 36 hours after injury. In addition, other studies have found a higher mortality rate (5%-15%) for patients with bilateral femur fractures than for patients with only one fracture.^7,12,13 Patients with a floating knee injury (ipsilateral tibia and femur fractures) are at higher risk for FES and have higher overall morbidity and mortality rates in comparison with patients with an isolated femur or tibia fracture, though the increased risk has not been quantified.

Review of Case Literature: FES With CFE

Few cases of FES with symptomatic CFE in the setting of long-bone fracture or long-bone surgery have been reported in the literature. There is wide variation in the development of FES with respect to preoperative or postoperative status and mechanism of injury. Duran and colleagues¹⁴ described a 20-year-old man with ipsilateral tibia and femur fractures caused by gunshots. Twenty-four hours after presentation, he developed tonic-clonic seizures and the classic triad of rash, hypoxia, and altered mental status. MRI confirmed CFE secondary to FES. The patient was optimized neurologically before definitive fixation and was discharged with minimal neurologic deficits on POD-27. Chang and colleagues¹⁵ and Yeo and colleagues¹⁶ described CFE in patients who underwent bilateral total knee arthroplasty. Symptoms developed 9 hours and 2 days after surgery, respectively. Both patients had fat emboli in the lungs and brain, underwent intensive care treatment, and recovered from the initial insult. After discharge at 44 days and 2 weeks, respectively, they fully recovered.

Other patients with CFE have had less favorable outcomes. Chen and colleagues⁶ reported the case of a 31-year-old man who sustained closed femur and tibia fractures in an automobile collision and experienced an acute decline in neurologic status 1 hour after arrival in the emergency department. The patient was intubated, CFE was diagnosed on the basis of MRI findings, and the orthopedic injuries were treated with external fixation. After 2 weeks, the patient was discharged with persistent neurologic deficits and the need for long-term tube feeding. Walshe and colleagues¹⁷ reported the case of a 19-year-old woman who sustained multiple long-bone injuries and traumatic brain injury and showed fat emboli on MRI. The patient experienced brain herniation while in the intensive care unit and later was declared brain-dead. According to the literature, it is important to maintain high suspicion for FES and possible CFE in the setting of high-energy fracture but also to be aware that FES may develop even with nondisplaced fracture or with reaming of the intramedullary canal in elective total joint arthroplasty.¹⁸

Pathophysiology of Fat Embolism Syndrome

The pathophysiology of FES and specifically of CFE is not widely understood. Two main theories on the development of FES have been advanced.

The mechanical theory suggests that exposing intramedullary long-bone contents allows fat to mobilize into the bloodstream.¹⁹ This occurs in the setting of long-bone fracture and in canal preparation during joint replacement surgery. More fat extravasates into the venous system after femur fracture than after tibia fracture, which accounts for the higher risk for FES in femoral shaft fractures and the even higher risk in concomitant femur and tibia fractures.⁴ In addition to there being a risk of fat embolism from the fracture itself, placing the patient in traction or reaming the intramedullary canal may exacerbate this effect by increased extravasation of fat from the medullary canal. With extravasation of fatty bone marrow into the venous system, fat emboli are free to travel back to the lungs, where they can cause infarcts within the lung parenchyma.

In the mechanical theory, presence of PFO may allow fat globules to pass into the systemic circulation and cause end-organ emboli. In the event of cerebral emboli, neurologic symptoms may vary widely and may include diffuse encephalopathy and global deficits.²⁰ Dog studies have found a possible mechanism for CFE in the absence of PFO. One such study, which used femoral pressurization to replicate cemented femoral arthroplasty, found that many fat globules had traversed the lungs after release into bone marrow,²¹ supporting the theory that fat droplets can traverse the pulmonary system without sequestration in the lung parenchyma. Riding and colleagues²² reported finding pulmonary arteriovenous shunts, which are thought to allow CFE to occur in the absence of PFO. More studies are needed to determine the prevalence of shunts and their overall contribution to CFE development in patients with long-bone fracture.

The biochemical theory holds that bodily trauma induces the release of free fatty acids (FFAs) from the capillaries into the bloodstream.²³ This stress response is mediated by catecholamines, which activate the adenyl cyclase pathway, which activates lipase, which hydrolyzes stored triglycerides to FFAs and glycerol. The concentration of circulating FFA was increased in 9 of 10 patients in one study.²³ Increased FFAs in the bloodstream can accelerate local and end-organ clotting, leading to thrombocytopenia and endothelial injury. In addition, patients with hypercoagulable diseases are at higher risk for postoperative thromboembolism.²⁴ However, with a negative hypercoagulable work-up and with negative chest helical CT and EKG, which did not demonstrate PFO, the explanation for CFE in our patient may more likely reside with the arteriovenous shunt theory proposed by Riding and colleagues.²²

Diagnosis and Treatment

Proper care of orthopedic patients who potentially have FES/CFE involves prompt diagnosis, immediate symptomatic care, and early coordination with neurology and medical services to rule out other causes of symptoms. Obtaining advanced imaging to rule out other potential causes and to confirm the diagnosis is crucial. The patient in this case report did not exhibit any focal neurologic deficits, but emergent CT of the brain was indicated to rule out a hemorrhagic event. If a stroke secondary to FES is clinically suspected, MRI should be obtained as soon as possible. Multiple studies have found that the “starfield” pattern, which is best seen as multiple punctate hyperintensities on T2 imaging, is the typical radiographic manifestation of CFE.⁹ This applies to patients who are in the 24- to 72-hour window after long-bone fracture or fixation and who fit Gurd and Wilson¹ criteria or Lindeque^1,2criteria, or who exhibit a change in mental status but have a negative CT scan of the brain, as was the case with our patient. Once the diagnosis is made, treatment involves addressing the symptoms (Figure 4).

Fat Embolism Syndrome in Reamed and Unreamed Nailing

Over the past several decades, the number of long bones fixed with intramedullary nails has increased significantly.²⁶ There is debate regarding whether use of reamed intramedullary nails increases the risk of fat emboli relative to use of unreamed nails, but multiple studies have found no significant difference.^26,27 Pulmonary shunting occurs in both reamed and unreamed nailing; neither technique has an advantage in terms of cardiopulmonary complications. In multiple studies, reamed nails have the advantage of improved healing rates.²⁷ A sheep study compared reamed and unreamed femoral nailing.²⁸ After nailing, sheep lungs were examined histologically for the presence of bone marrow fat embolism. The embolism rate was higher with unreamed nailing (10.25%) than with reamed nailing (6.66%). One large study of the adverse effects of reamed and unreamed nailing in 1226 patients with tibial shaft fracture found that those with open fractures had higher rates of a negative event (nonunion, infection, fasciotomy, hardware failure, need for dynamization) after reamed nailing.²⁹ Patients with closed fractures had fewer events after reamed nailing. The authors concluded there is a potential benefit in outcome with reamed intramedullary nailing in patients with closed tibial shaft fractures, but they did not comment on development of FES. In a study of the effect of subject position on intramedullary pressure and fat embolism release, dogs were positioned either supine or lateral for tibial and femoral reaming.³⁰ The authors measured various physiologic parameters, including cardiac output, pulmonary arterial wedge pressure, arterial and venous blood gas, and blood cell counts. There were no statistically significant differences in values between the 2 groups in any variable, indicating that position does not affect FES development in the orthopedic trauma setting.

Conclusion

FES and CFE are potential devastating sequelae of both long-bone fracture and long-bone instrumentation. It is important to recognize these entities in the acute setting and to consider them in the differential diagnosis of a trauma or postoperative patient who experiences sudden onset of altered mental status with or without dyspnea or a petechial rash. If CFE is suspected, early advanced imaging (including urgent MRI) should be obtained with rapid involvement of a multidisciplinary team that can optimize the chance for successful recovery of both neurologic and physical function. The best treatment, early prevention and diagnosis, maximizes care of symptoms. As is evidenced in this case report, rapid diagnosis and treatment often result in recovery from a majority of the symptoms of FES and CFE.

Am J Orthop. 2016;45(7):E515-E521. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Septic arthritis is a common orthopedic emergency. The most common causative organism is Staphylococcus aureus. Mycotic infections, such as those involving Candida organisms, are much less common but just as debilitating. Delayed diagnosis of septic arthritis caused by Candida infection may result in increased morbidity, making treatment more challenging. Here we report a case of Candida albicans septic arthritis of the ankle and subtalar joint in a patient with diabetes mellitus (DM) and rheumatoid arthritis (RA). The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 52-year-old woman with type 2 DM (requiring subcutaneous insulin analogue therapy) and RA presented to a local emergency department with a 3-day history of right ankle pain after having the subtalar joint injected with steroid by a rheumatologist 4 weeks earlier. For about 2 weeks, there was purulent discharge from the peroneal sheath. The patient’s RA was being treated with prednisolone (maintenance therapy). Physical examination revealed low-grade pyrexia (37.8°C) and difficulty bearing full weight on the ankle. Clinically, the joint was not erythematous, but active and passive movements were painful. Blood tests revealed a C-reactive protein level of 98 mg/dL and a white blood cell (WBC) count of 11.3 × 10⁹/L. Erythrocyte sedimentation rate (ESR) was not checked. The ankle underwent magnetic resonance imaging (Figures A-D).

Mycotic screening of the fluid was positive for C albicans. The patient was referred to the orthopedic team, which performed urgent arthroscopic surgical débridement, biopsy, and washout of the subtalar joint. After surgery, a 6-week course of antifungal therapy with anidulafungin was started, per specialist microbiology advice.

The septic ankle was successfully managed with arthroscopic surgical débridement followed by treatment with anidulafungin. The patient continued to make good progress and was weight-bearing when discharged home from the orthopedic unit.

Discussion

Worldwide, about 1 in 6 people has arthritis, which affects daily lifestyle and reduces quality of life. Degenerative, inflammatory, and septic arthritis each has its management challenges.¹

Septic arthritis is an acute infection of the joint, usually of bacterial etiology. It can present as a polyarticular arthropathy (~15% of cases),^2,3 but a monoarthropathy of the hip, knee, or ankle is more common.⁴The Kocher criteria are often applied to cases of suspected septic arthritis of joints, even though they were initially used to distinguish septic arthritis from transient synovitis in pediatric hip joints.⁵ Kocher and colleagues⁵ reported 4 key clinical criteria: inability to bear weight, WBC count over 12 × 10⁹/L, ESR over 40 mm/h, and temperature over 38.5°C. When all 4 criteria are met, the predictive value is 99.6%. These criteria are now widely applied to adult joints, and not only the hips.

In septic arthritis, the most common causative pathogen is S aureus.^3,6Streptococcus, Neisseria, and Pseudomonas also are common.⁷ Although much rarer, Candida variants and other mycotic pathogens have been implicated as well.⁸C albicans is a well-known fungus that colonizes mucosal surfaces. Research indicates increased oral C albicans colonization in rheumatoid patients.⁹ Although most Candida septic arthritis cases are caused by C albicans, there is no large body of data showing the true incidence of fungal pathogens in septic arthritis.

Our literature search yielded 2 case reports on Candida septic arthritis involving the ankle, but the causative organisms were Candida parapsilosis and Candida glabrata.^9,10 Cases of Candida septic arthritis involving the knee or shoulder have also been reported.^11-15 Case reports demonstrate that Candida fungal arthritis is extremely rare.⁹ Etiology reportedly includes direct intra-articular inoculation by surgery or secondary to hematogenous seeding, particularly in immunocompromised patients.¹⁰ Risk factors include immunosuppression and joint suppression. DM and RA are common comorbidities in patients with septic arthritis.^6,16 The pathophysiology of RA is inflammatory pannus formation of the periarticular surface with subsequent articular cartilage destruction and erosion, as well as progressive deformity and functional debilitation.¹Patients with DM are at increased risk for developing fungal and other infections. Factors increasing this risk include disruption of skin-barrier integrity; reduced peripheral oxygen and blood supply, which also disrupts antibiotic delivery; and hyperglycemia-induced reduction in antibody function and disruption of phagocytosis and chemotaxis.¹⁷Fungi are eukaryotic, and infections caused by these organisms are difficult to treat.¹⁸ As fungal infections are more prevalent among immunosuppressed patients, they often result in prolonged treatment without guarantee of eradication, as spores may persist subclinically.

Literature on C albicans septic arthritis is lacking in general but especially in rheumatoid patients. Delayed diagnosis and suboptimal treatment may result in fungal osteomyelitis. There is little evidence on treating this rare fungal complication, and outcomes historically have been poor.¹⁹In an animal model, Marijnissen and colleagues²⁰ found that C albicans infection can increase destruction in an arthritic joint by cytokine environment modification. The result was advanced destruction of the joint and debilitation. For disease management, the authors considered these essential: early diagnosis, prompt treatment, and, as indicated, surgical débridement.

Treatment of Candida septic arthritis largely involves use of antifungal medication, either with surgical débridement, as in our patient’s case, or without. Which antifungal medication to use should be based on sensitivities, identified from wound aspirate, and microbiology advice about treatment duration. The antibiotic should be a broad-spectrum antifungal cover, in keeping with local antibiotic prescribing guidelines, which can be refined once definitive organism culture and sensitivity results are known. However, early aggressive treatment is essential. Periprosthetic fungal infection is rarely resolved without implant removal.²¹

Conclusion

This case reflects the complexities of septic arthritis caused by atypical pathogens and highlights the need for clinical vigilance in the setting of comorbidities, such as DM and RA. Failure to consider the diagnosis early on might result in delayed and inadequate treatment, increased joint destruction, and, potentially, osteomyelitis with subsequent increased morbidity. Early diagnosis (based on joint aspirate findings), surgical débridement, and prolonged aggressive treatment with antifungal medication are the mainstays of treatment.

Am J Orthop. 2016;45(7):E478-E480. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Septic arthritis is a common orthopedic emergency. The most common causative organism is Staphylococcus aureus. Mycotic infections, such as those involving Candida organisms, are much less common but just as debilitating. Delayed diagnosis of septic arthritis caused by Candida infection may result in increased morbidity, making treatment more challenging. Here we report a case of Candida albicans septic arthritis of the ankle and subtalar joint in a patient with diabetes mellitus (DM) and rheumatoid arthritis (RA). The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 52-year-old woman with type 2 DM (requiring subcutaneous insulin analogue therapy) and RA presented to a local emergency department with a 3-day history of right ankle pain after having the subtalar joint injected with steroid by a rheumatologist 4 weeks earlier. For about 2 weeks, there was purulent discharge from the peroneal sheath. The patient’s RA was being treated with prednisolone (maintenance therapy). Physical examination revealed low-grade pyrexia (37.8°C) and difficulty bearing full weight on the ankle. Clinically, the joint was not erythematous, but active and passive movements were painful. Blood tests revealed a C-reactive protein level of 98 mg/dL and a white blood cell (WBC) count of 11.3 × 10⁹/L. Erythrocyte sedimentation rate (ESR) was not checked. The ankle underwent magnetic resonance imaging (Figures A-D).

Mycotic screening of the fluid was positive for C albicans. The patient was referred to the orthopedic team, which performed urgent arthroscopic surgical débridement, biopsy, and washout of the subtalar joint. After surgery, a 6-week course of antifungal therapy with anidulafungin was started, per specialist microbiology advice.

The septic ankle was successfully managed with arthroscopic surgical débridement followed by treatment with anidulafungin. The patient continued to make good progress and was weight-bearing when discharged home from the orthopedic unit.

Discussion

Worldwide, about 1 in 6 people has arthritis, which affects daily lifestyle and reduces quality of life. Degenerative, inflammatory, and septic arthritis each has its management challenges.¹

Septic arthritis is an acute infection of the joint, usually of bacterial etiology. It can present as a polyarticular arthropathy (~15% of cases),^2,3 but a monoarthropathy of the hip, knee, or ankle is more common.⁴The Kocher criteria are often applied to cases of suspected septic arthritis of joints, even though they were initially used to distinguish septic arthritis from transient synovitis in pediatric hip joints.⁵ Kocher and colleagues⁵ reported 4 key clinical criteria: inability to bear weight, WBC count over 12 × 10⁹/L, ESR over 40 mm/h, and temperature over 38.5°C. When all 4 criteria are met, the predictive value is 99.6%. These criteria are now widely applied to adult joints, and not only the hips.

In septic arthritis, the most common causative pathogen is S aureus.^3,6Streptococcus, Neisseria, and Pseudomonas also are common.⁷ Although much rarer, Candida variants and other mycotic pathogens have been implicated as well.⁸C albicans is a well-known fungus that colonizes mucosal surfaces. Research indicates increased oral C albicans colonization in rheumatoid patients.⁹ Although most Candida septic arthritis cases are caused by C albicans, there is no large body of data showing the true incidence of fungal pathogens in septic arthritis.

Our literature search yielded 2 case reports on Candida septic arthritis involving the ankle, but the causative organisms were Candida parapsilosis and Candida glabrata.^9,10 Cases of Candida septic arthritis involving the knee or shoulder have also been reported.^11-15 Case reports demonstrate that Candida fungal arthritis is extremely rare.⁹ Etiology reportedly includes direct intra-articular inoculation by surgery or secondary to hematogenous seeding, particularly in immunocompromised patients.¹⁰ Risk factors include immunosuppression and joint suppression. DM and RA are common comorbidities in patients with septic arthritis.^6,16 The pathophysiology of RA is inflammatory pannus formation of the periarticular surface with subsequent articular cartilage destruction and erosion, as well as progressive deformity and functional debilitation.¹Patients with DM are at increased risk for developing fungal and other infections. Factors increasing this risk include disruption of skin-barrier integrity; reduced peripheral oxygen and blood supply, which also disrupts antibiotic delivery; and hyperglycemia-induced reduction in antibody function and disruption of phagocytosis and chemotaxis.¹⁷Fungi are eukaryotic, and infections caused by these organisms are difficult to treat.¹⁸ As fungal infections are more prevalent among immunosuppressed patients, they often result in prolonged treatment without guarantee of eradication, as spores may persist subclinically.

Literature on C albicans septic arthritis is lacking in general but especially in rheumatoid patients. Delayed diagnosis and suboptimal treatment may result in fungal osteomyelitis. There is little evidence on treating this rare fungal complication, and outcomes historically have been poor.¹⁹In an animal model, Marijnissen and colleagues²⁰ found that C albicans infection can increase destruction in an arthritic joint by cytokine environment modification. The result was advanced destruction of the joint and debilitation. For disease management, the authors considered these essential: early diagnosis, prompt treatment, and, as indicated, surgical débridement.

Treatment of Candida septic arthritis largely involves use of antifungal medication, either with surgical débridement, as in our patient’s case, or without. Which antifungal medication to use should be based on sensitivities, identified from wound aspirate, and microbiology advice about treatment duration. The antibiotic should be a broad-spectrum antifungal cover, in keeping with local antibiotic prescribing guidelines, which can be refined once definitive organism culture and sensitivity results are known. However, early aggressive treatment is essential. Periprosthetic fungal infection is rarely resolved without implant removal.²¹

Conclusion

This case reflects the complexities of septic arthritis caused by atypical pathogens and highlights the need for clinical vigilance in the setting of comorbidities, such as DM and RA. Failure to consider the diagnosis early on might result in delayed and inadequate treatment, increased joint destruction, and, potentially, osteomyelitis with subsequent increased morbidity. Early diagnosis (based on joint aspirate findings), surgical débridement, and prolonged aggressive treatment with antifungal medication are the mainstays of treatment.

Am J Orthop. 2016;45(7):E478-E480. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

Septic arthritis is a common orthopedic emergency. The most common causative organism is Staphylococcus aureus. Mycotic infections, such as those involving Candida organisms, are much less common but just as debilitating. Delayed diagnosis of septic arthritis caused by Candida infection may result in increased morbidity, making treatment more challenging. Here we report a case of Candida albicans septic arthritis of the ankle and subtalar joint in a patient with diabetes mellitus (DM) and rheumatoid arthritis (RA). The patient provided written informed consent for print and electronic publication of this case report.

Case Report

A 52-year-old woman with type 2 DM (requiring subcutaneous insulin analogue therapy) and RA presented to a local emergency department with a 3-day history of right ankle pain after having the subtalar joint injected with steroid by a rheumatologist 4 weeks earlier. For about 2 weeks, there was purulent discharge from the peroneal sheath. The patient’s RA was being treated with prednisolone (maintenance therapy). Physical examination revealed low-grade pyrexia (37.8°C) and difficulty bearing full weight on the ankle. Clinically, the joint was not erythematous, but active and passive movements were painful. Blood tests revealed a C-reactive protein level of 98 mg/dL and a white blood cell (WBC) count of 11.3 × 10⁹/L. Erythrocyte sedimentation rate (ESR) was not checked. The ankle underwent magnetic resonance imaging (Figures A-D).

Mycotic screening of the fluid was positive for C albicans. The patient was referred to the orthopedic team, which performed urgent arthroscopic surgical débridement, biopsy, and washout of the subtalar joint. After surgery, a 6-week course of antifungal therapy with anidulafungin was started, per specialist microbiology advice.

The septic ankle was successfully managed with arthroscopic surgical débridement followed by treatment with anidulafungin. The patient continued to make good progress and was weight-bearing when discharged home from the orthopedic unit.

Discussion

Worldwide, about 1 in 6 people has arthritis, which affects daily lifestyle and reduces quality of life. Degenerative, inflammatory, and septic arthritis each has its management challenges.¹

Septic arthritis is an acute infection of the joint, usually of bacterial etiology. It can present as a polyarticular arthropathy (~15% of cases),^2,3 but a monoarthropathy of the hip, knee, or ankle is more common.⁴The Kocher criteria are often applied to cases of suspected septic arthritis of joints, even though they were initially used to distinguish septic arthritis from transient synovitis in pediatric hip joints.⁵ Kocher and colleagues⁵ reported 4 key clinical criteria: inability to bear weight, WBC count over 12 × 10⁹/L, ESR over 40 mm/h, and temperature over 38.5°C. When all 4 criteria are met, the predictive value is 99.6%. These criteria are now widely applied to adult joints, and not only the hips.

In septic arthritis, the most common causative pathogen is S aureus.^3,6Streptococcus, Neisseria, and Pseudomonas also are common.⁷ Although much rarer, Candida variants and other mycotic pathogens have been implicated as well.⁸C albicans is a well-known fungus that colonizes mucosal surfaces. Research indicates increased oral C albicans colonization in rheumatoid patients.⁹ Although most Candida septic arthritis cases are caused by C albicans, there is no large body of data showing the true incidence of fungal pathogens in septic arthritis.

Our literature search yielded 2 case reports on Candida septic arthritis involving the ankle, but the causative organisms were Candida parapsilosis and Candida glabrata.^9,10 Cases of Candida septic arthritis involving the knee or shoulder have also been reported.^11-15 Case reports demonstrate that Candida fungal arthritis is extremely rare.⁹ Etiology reportedly includes direct intra-articular inoculation by surgery or secondary to hematogenous seeding, particularly in immunocompromised patients.¹⁰ Risk factors include immunosuppression and joint suppression. DM and RA are common comorbidities in patients with septic arthritis.^6,16 The pathophysiology of RA is inflammatory pannus formation of the periarticular surface with subsequent articular cartilage destruction and erosion, as well as progressive deformity and functional debilitation.¹Patients with DM are at increased risk for developing fungal and other infections. Factors increasing this risk include disruption of skin-barrier integrity; reduced peripheral oxygen and blood supply, which also disrupts antibiotic delivery; and hyperglycemia-induced reduction in antibody function and disruption of phagocytosis and chemotaxis.¹⁷Fungi are eukaryotic, and infections caused by these organisms are difficult to treat.¹⁸ As fungal infections are more prevalent among immunosuppressed patients, they often result in prolonged treatment without guarantee of eradication, as spores may persist subclinically.

Literature on C albicans septic arthritis is lacking in general but especially in rheumatoid patients. Delayed diagnosis and suboptimal treatment may result in fungal osteomyelitis. There is little evidence on treating this rare fungal complication, and outcomes historically have been poor.¹⁹In an animal model, Marijnissen and colleagues²⁰ found that C albicans infection can increase destruction in an arthritic joint by cytokine environment modification. The result was advanced destruction of the joint and debilitation. For disease management, the authors considered these essential: early diagnosis, prompt treatment, and, as indicated, surgical débridement.

Treatment of Candida septic arthritis largely involves use of antifungal medication, either with surgical débridement, as in our patient’s case, or without. Which antifungal medication to use should be based on sensitivities, identified from wound aspirate, and microbiology advice about treatment duration. The antibiotic should be a broad-spectrum antifungal cover, in keeping with local antibiotic prescribing guidelines, which can be refined once definitive organism culture and sensitivity results are known. However, early aggressive treatment is essential. Periprosthetic fungal infection is rarely resolved without implant removal.²¹

Conclusion

This case reflects the complexities of septic arthritis caused by atypical pathogens and highlights the need for clinical vigilance in the setting of comorbidities, such as DM and RA. Failure to consider the diagnosis early on might result in delayed and inadequate treatment, increased joint destruction, and, potentially, osteomyelitis with subsequent increased morbidity. Early diagnosis (based on joint aspirate findings), surgical débridement, and prolonged aggressive treatment with antifungal medication are the mainstays of treatment.

Am J Orthop. 2016;45(7):E478-E480. Copyright Frontline Medical Communications Inc. 2016. All rights reserved.

An 89-year-old man presented to the ED with facial trauma due to a mechanical fall after losing his balance on uneven pavement and hitting the right side of his face. Physical examination revealed an ecchymosis inferior to the right eye and tenderness to palpation at the right maxilla and bilateral nasolabial folds. Maxillofacial computed tomography (CT) was ordered for further evaluation; representative images are presented above (Figure 1a and 1b).

What is the diagnosis?

Answer

A noncontrast CT of the maxillofacial bones demonstrated acute fractures through the bilateral pterygoid plates (white arrows, Figure 2a). The fractures extended through the medial and lateral walls of the bilateral maxillary sinuses (red arrows, Figure 2a), and propagated to the frontal processes of the maxilla (red arrows, Figure 2b), extending toward the alveolar process, indicating involvement of the anterolateral margin of the nasal fossa. The full extent of the fracture is best seen on a 3D-reconstructed image (red arrows, Figure 3). Additional images (not presented here) confirmed no fracture involvement of the orbital floors, nasal bones, or zygomatic arches. Expected posttraumatic hemorrhage was appreciated within the maxillary sinuses (white asterisks, Figure 2a).

Le Fort Fractures

The findings described above are characteristic of a Le Fort I fracture pattern. Initially described in 1901 by René Le Fort, a French surgeon, the Le Fort classification system details somewhat predictable midface fracture patterns resulting in various degrees of craniofacial disassociation.¹ Using weights that were dropped on cadaveric heads, Le Fort discovered that the pterygoid plates must be disrupted in order for the midface facial bones to separate from the skull base. As such, when diagnosing a Le Fort fracture, fracture of the pterygoid plate must be present, regardless of the fracture type (Le Fort I, II, and III).²

Le Fort I Fracture. This fracture pattern (red line, Figure 4) is referred to as a “floating palate” and involves separation of the hard palate from the skull base via fracture extension from the pterygoid plates into the maxillary sinus walls, as demonstrated in this case. The key distinguisher of the Le Fort I pattern is involvement of the anterolateral margin of the nasal fossa.²

Le Fort II Fracture. This fracture pattern (blue line, Figure 4) describes a “floating maxilla” wherein the pterygoid plate fractures are met with a pyramidal-type fracture pattern of the midface. The maxillary teeth form the base of the pyramid, and the fracture extends superiorly through the infraorbital rims bilaterally and toward the nasofrontal suture.^2,3 Le Fort II fractures result in the maxilla floating freely from the rest of the midface and skull base.

Le Fort III Fracture. This fracture pattern (green lines, Figure 4) describes a “floating face” with complete craniofacial disjunction resulting from fracture of the pterygoid plates, nasofrontal suture, maxillofrontal suture, orbital wall, and zygomatic arch/zygomaticofrontal suture.^2,3

It is important to note that midface trauma represents a complex spectrum of injuries, and Le Fort fractures only account for a small percentage of facial bone fractures that present through Level 1 trauma centers.² Le Fort fracture patterns can coexist with other fracture patterns and also can be seen in combination with each other. For example, one side of the face may demonstrate a Le Fort II pattern while the other side concurrently demonstrates a Le Fort III pattern. Though not robust enough for complete description of and surgical planning for facial fractures, this classification system is a succinct and well-accepted means of describing major fracture planes.

An 89-year-old man presented to the ED with facial trauma due to a mechanical fall after losing his balance on uneven pavement and hitting the right side of his face. Physical examination revealed an ecchymosis inferior to the right eye and tenderness to palpation at the right maxilla and bilateral nasolabial folds. Maxillofacial computed tomography (CT) was ordered for further evaluation; representative images are presented above (Figure 1a and 1b).

What is the diagnosis?

Answer

A noncontrast CT of the maxillofacial bones demonstrated acute fractures through the bilateral pterygoid plates (white arrows, Figure 2a). The fractures extended through the medial and lateral walls of the bilateral maxillary sinuses (red arrows, Figure 2a), and propagated to the frontal processes of the maxilla (red arrows, Figure 2b), extending toward the alveolar process, indicating involvement of the anterolateral margin of the nasal fossa. The full extent of the fracture is best seen on a 3D-reconstructed image (red arrows, Figure 3). Additional images (not presented here) confirmed no fracture involvement of the orbital floors, nasal bones, or zygomatic arches. Expected posttraumatic hemorrhage was appreciated within the maxillary sinuses (white asterisks, Figure 2a).

Le Fort Fractures

The findings described above are characteristic of a Le Fort I fracture pattern. Initially described in 1901 by René Le Fort, a French surgeon, the Le Fort classification system details somewhat predictable midface fracture patterns resulting in various degrees of craniofacial disassociation.¹ Using weights that were dropped on cadaveric heads, Le Fort discovered that the pterygoid plates must be disrupted in order for the midface facial bones to separate from the skull base. As such, when diagnosing a Le Fort fracture, fracture of the pterygoid plate must be present, regardless of the fracture type (Le Fort I, II, and III).²

Le Fort I Fracture. This fracture pattern (red line, Figure 4) is referred to as a “floating palate” and involves separation of the hard palate from the skull base via fracture extension from the pterygoid plates into the maxillary sinus walls, as demonstrated in this case. The key distinguisher of the Le Fort I pattern is involvement of the anterolateral margin of the nasal fossa.²

Le Fort II Fracture. This fracture pattern (blue line, Figure 4) describes a “floating maxilla” wherein the pterygoid plate fractures are met with a pyramidal-type fracture pattern of the midface. The maxillary teeth form the base of the pyramid, and the fracture extends superiorly through the infraorbital rims bilaterally and toward the nasofrontal suture.^2,3 Le Fort II fractures result in the maxilla floating freely from the rest of the midface and skull base.

Le Fort III Fracture. This fracture pattern (green lines, Figure 4) describes a “floating face” with complete craniofacial disjunction resulting from fracture of the pterygoid plates, nasofrontal suture, maxillofrontal suture, orbital wall, and zygomatic arch/zygomaticofrontal suture.^2,3

It is important to note that midface trauma represents a complex spectrum of injuries, and Le Fort fractures only account for a small percentage of facial bone fractures that present through Level 1 trauma centers.² Le Fort fracture patterns can coexist with other fracture patterns and also can be seen in combination with each other. For example, one side of the face may demonstrate a Le Fort II pattern while the other side concurrently demonstrates a Le Fort III pattern. Though not robust enough for complete description of and surgical planning for facial fractures, this classification system is a succinct and well-accepted means of describing major fracture planes.

An 89-year-old man presented to the ED with facial trauma due to a mechanical fall after losing his balance on uneven pavement and hitting the right side of his face. Physical examination revealed an ecchymosis inferior to the right eye and tenderness to palpation at the right maxilla and bilateral nasolabial folds. Maxillofacial computed tomography (CT) was ordered for further evaluation; representative images are presented above (Figure 1a and 1b).

What is the diagnosis?

Answer

A noncontrast CT of the maxillofacial bones demonstrated acute fractures through the bilateral pterygoid plates (white arrows, Figure 2a). The fractures extended through the medial and lateral walls of the bilateral maxillary sinuses (red arrows, Figure 2a), and propagated to the frontal processes of the maxilla (red arrows, Figure 2b), extending toward the alveolar process, indicating involvement of the anterolateral margin of the nasal fossa. The full extent of the fracture is best seen on a 3D-reconstructed image (red arrows, Figure 3). Additional images (not presented here) confirmed no fracture involvement of the orbital floors, nasal bones, or zygomatic arches. Expected posttraumatic hemorrhage was appreciated within the maxillary sinuses (white asterisks, Figure 2a).

Le Fort Fractures

The findings described above are characteristic of a Le Fort I fracture pattern. Initially described in 1901 by René Le Fort, a French surgeon, the Le Fort classification system details somewhat predictable midface fracture patterns resulting in various degrees of craniofacial disassociation.¹ Using weights that were dropped on cadaveric heads, Le Fort discovered that the pterygoid plates must be disrupted in order for the midface facial bones to separate from the skull base. As such, when diagnosing a Le Fort fracture, fracture of the pterygoid plate must be present, regardless of the fracture type (Le Fort I, II, and III).²

Le Fort I Fracture. This fracture pattern (red line, Figure 4) is referred to as a “floating palate” and involves separation of the hard palate from the skull base via fracture extension from the pterygoid plates into the maxillary sinus walls, as demonstrated in this case. The key distinguisher of the Le Fort I pattern is involvement of the anterolateral margin of the nasal fossa.²

Le Fort II Fracture. This fracture pattern (blue line, Figure 4) describes a “floating maxilla” wherein the pterygoid plate fractures are met with a pyramidal-type fracture pattern of the midface. The maxillary teeth form the base of the pyramid, and the fracture extends superiorly through the infraorbital rims bilaterally and toward the nasofrontal suture.^2,3 Le Fort II fractures result in the maxilla floating freely from the rest of the midface and skull base.

Le Fort III Fracture. This fracture pattern (green lines, Figure 4) describes a “floating face” with complete craniofacial disjunction resulting from fracture of the pterygoid plates, nasofrontal suture, maxillofrontal suture, orbital wall, and zygomatic arch/zygomaticofrontal suture.^2,3

It is important to note that midface trauma represents a complex spectrum of injuries, and Le Fort fractures only account for a small percentage of facial bone fractures that present through Level 1 trauma centers.² Le Fort fracture patterns can coexist with other fracture patterns and also can be seen in combination with each other. For example, one side of the face may demonstrate a Le Fort II pattern while the other side concurrently demonstrates a Le Fort III pattern. Though not robust enough for complete description of and surgical planning for facial fractures, this classification system is a succinct and well-accepted means of describing major fracture planes.