Prince Adotama, MD

To the Editor:

A 73-year-old man was admitted to the hospital with progressive abdominal and hip pain of several weeks’ duration that was accompanied by unilateral swelling of the left leg. He had a medical history of hypertension, hyperlipidemia, and prediabetes. Computed tomography (CT) showed extensive intra-abdominal, retroperitoneal, and pelvic lymphadenopathy in addition to poorly defined hepatic lesions.

A CT-guided core biopsy of a left inguinal lymph node showed Burkitt lymphoma. Fluorescence in situ hybridization was positive for oncogene c-MYC rearrangement on chromosome 8q24 and negative for B-cell lymphoma 2 (BCL2) and B-cell lymphoma 6 (BCL6) gene rearrangements. Flow cytometry demonstrated an aberrant population of κ light chain-restricted CD5⁻CD10⁺ B lymphocytes.

The patient’s overall disease burden was consistent with stage IV Burkitt lymphoma. R-miniCHOP chemotherapy—rituximab plus a reduced dose of cyclophosphamide, doxorubicin, vincristine sulfate, and prednisone—was initiated. Approximately 2 weeks after chemotherapy was initiated, the patient developed a firm erythematous eruption on the left hip (Figure 1A). His regimen was then switched to R-EPOCH—rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin—at the time of discharge, and he was referred to dermatology due to an initial concern of an adverse reaction to R-EPOCH chemotherapy. The patient denied any pain, pruritus, or irritation. Physical examination showed multifocal, subcutaneous, indurated, erythematous and violaceous nodules without epidermal changes. Some nodules on the lateral aspect of the hip coalesced to form firm plaques.

A punch biopsy specimen showed markedly atypical lymphocytes with enlarged nuclei and scant cytoplasm present throughout the dermis (Figures 2A and 2B). Numerous apoptotic cells and cellular debris were seen. Immunohistochemical staining demonstrated that the lymphocytic infiltrate comprised CD79a⁺ B cells that were positive for Bcl-6 and CD10 and negative for Bcl-2 (Figures 2C and 2D). There also was diminished focal expression of CD20. Ki-67 protein staining was intensely positive and demonstrated a very high proliferative index.

Taken together, these findings were consistent with a diagnosis of cutaneous metastasis of Burkitt lymphoma. The patient’s cutaneous lesions improved after continued aggressive chemotherapy. At follow-up 2 weeks after biopsy, he was receiving his second round of R-EPOCH chemotherapy with appreciable regression of skin lesions (Figure 1B). However, he then developed right-side double vision, ptosis, and right-side facial paresthesia. Although magnetic resonance imaging of the brain and lumbar puncture did not show evidence of central nervous system involvement, the chemotherapy regimen was switched to dose-adjusted CVAD-R—hypercyclophosphamide, vincristine, doxorubicin hydrochloride, and dexamethasone plus rituximab—for empiric treatment of central nervous system disease. Although treatment was complicated by sepsis with extended-spectrum β-lactamase-producing Enterobacter cloacae, Burkitt lymphoma was found to be in remission after 3 cycles of CVAD-R and 5 months of chemotherapy.

Burkitt lymphoma is a B-cell non-Hodgkin malignancy caused by translocation of chromosome 8 and chromosome 14, leading to overexpression of c-MYC and subsequent hyperproliferation of B lymphocytes.^1,2 The disease is divided into 3 major categories: sporadic, endemic, and immunodeficiency related.³ The endemic variant is the most prevalent subtype in Africa and is associated with Plasmodium falciparum malaria; the sporadic variant is the most common subtype in the rest of the world.⁴

Burkitt lymphoma is highly aggressive and is characterized by unusually high rates of mitosis and apoptosis that result in abundant cellular debris and a distinctive starry-sky pattern on histopathology.^5,6 Extranodal metastasis is common,⁷ but cutaneous involvement is exceedingly rare, with only a few cases having been reported.^8-14 Cutaneous metastasis of Burkitt lymphoma often is associated with a high overall disease burden and poor prognosis.^8,11

Immunodeficiency-related Burkitt lymphoma is particularly aggressive. Notably, 3 of 7 (42.9%) reported cases of cutaneous Burkitt lymphoma occurred in HIV-positive patients.^11,13 In one case, cutaneous involvement was the first sign of relapsed disease that had been in remission.¹²

Although c-MYC rearrangement is required to make a diagnosis of Burkitt lymphoma, the disease also is present in a minority of cases of diffuse large B-cell lymphoma (DLBCL)(6%).¹⁵ Although DLBCL typically can be differentiated from Burkitt lymphoma by the large nuclear size and characteristic vesicular nuclei of B cells, few cases of DLBCL with c-MYC rearrangement histologically mimic Burkitt lymphoma. However, key features such as immunohistochemical staining for Bcl-2 and CD10 can be used to distinguish these 2 entities.¹⁶ Bcl-2 negativity and CD10 positivity, as seen in our patient, is considered more characteristic of Burkitt lymphoma. This staining pattern in combination with a high Ki-67 fraction (>95%) and the presence of monomorphic medium-sized cells is more consistent with a diagnosis of Burkitt lymphoma than of DLBCL.¹⁷

Earlier case reports have documented that cutaneous lesions of Burkitt lymphoma can occur in a variety of ways. Hematogenous spread is the likely route of metastasis for lesions distant to the primary site or those that have widespread distribution.¹⁸ Alternatively, other reports have suggested that cutaneous metastases can occur from local invasion and subcutaneous extension of malignant cells after a surgical procedure.^10,19 For example, cutaneous Burkitt lymphoma has been reported in the setting of celioscopy, occurring directly at the surgical site.¹⁹ In our patient, we believe that the route of metastatic spread likely was through subcutaneous invasion secondary to CT-guided core biopsy, which was supported by the observation that the onset of cutaneous manifestations was temporally related to the procedure and that the lesions occurred on the skin directly overlying the biopsy site.

In conclusion, we describe an exceedingly rare presentation of cutaneous Burkitt lymphoma in which a surgical procedure likely served as an inciting event that triggered seeding of malignant cells to the skin. Cutaneous spread of Burkitt lymphoma is infrequently reported; all such reports that provide long-term follow-up data have described it in association with high disease burden and often a lethal outcome.^8,11,12 Our patient had complete resolution of cutaneous lesions with chemotherapy. It is unclear if the presence of cutaneous lesions can serve as a prognostic indicator and requires further investigation. However, our case provides preliminary evidence to suggest that cutaneous metastases do not always represent aggressive disease and that cutaneous lesions may respond well to chemotherapy.

To the Editor:

A 73-year-old man was admitted to the hospital with progressive abdominal and hip pain of several weeks’ duration that was accompanied by unilateral swelling of the left leg. He had a medical history of hypertension, hyperlipidemia, and prediabetes. Computed tomography (CT) showed extensive intra-abdominal, retroperitoneal, and pelvic lymphadenopathy in addition to poorly defined hepatic lesions.

A CT-guided core biopsy of a left inguinal lymph node showed Burkitt lymphoma. Fluorescence in situ hybridization was positive for oncogene c-MYC rearrangement on chromosome 8q24 and negative for B-cell lymphoma 2 (BCL2) and B-cell lymphoma 6 (BCL6) gene rearrangements. Flow cytometry demonstrated an aberrant population of κ light chain-restricted CD5⁻CD10⁺ B lymphocytes.

The patient’s overall disease burden was consistent with stage IV Burkitt lymphoma. R-miniCHOP chemotherapy—rituximab plus a reduced dose of cyclophosphamide, doxorubicin, vincristine sulfate, and prednisone—was initiated. Approximately 2 weeks after chemotherapy was initiated, the patient developed a firm erythematous eruption on the left hip (Figure 1A). His regimen was then switched to R-EPOCH—rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin—at the time of discharge, and he was referred to dermatology due to an initial concern of an adverse reaction to R-EPOCH chemotherapy. The patient denied any pain, pruritus, or irritation. Physical examination showed multifocal, subcutaneous, indurated, erythematous and violaceous nodules without epidermal changes. Some nodules on the lateral aspect of the hip coalesced to form firm plaques.

A punch biopsy specimen showed markedly atypical lymphocytes with enlarged nuclei and scant cytoplasm present throughout the dermis (Figures 2A and 2B). Numerous apoptotic cells and cellular debris were seen. Immunohistochemical staining demonstrated that the lymphocytic infiltrate comprised CD79a⁺ B cells that were positive for Bcl-6 and CD10 and negative for Bcl-2 (Figures 2C and 2D). There also was diminished focal expression of CD20. Ki-67 protein staining was intensely positive and demonstrated a very high proliferative index.

Taken together, these findings were consistent with a diagnosis of cutaneous metastasis of Burkitt lymphoma. The patient’s cutaneous lesions improved after continued aggressive chemotherapy. At follow-up 2 weeks after biopsy, he was receiving his second round of R-EPOCH chemotherapy with appreciable regression of skin lesions (Figure 1B). However, he then developed right-side double vision, ptosis, and right-side facial paresthesia. Although magnetic resonance imaging of the brain and lumbar puncture did not show evidence of central nervous system involvement, the chemotherapy regimen was switched to dose-adjusted CVAD-R—hypercyclophosphamide, vincristine, doxorubicin hydrochloride, and dexamethasone plus rituximab—for empiric treatment of central nervous system disease. Although treatment was complicated by sepsis with extended-spectrum β-lactamase-producing Enterobacter cloacae, Burkitt lymphoma was found to be in remission after 3 cycles of CVAD-R and 5 months of chemotherapy.

Burkitt lymphoma is a B-cell non-Hodgkin malignancy caused by translocation of chromosome 8 and chromosome 14, leading to overexpression of c-MYC and subsequent hyperproliferation of B lymphocytes.^1,2 The disease is divided into 3 major categories: sporadic, endemic, and immunodeficiency related.³ The endemic variant is the most prevalent subtype in Africa and is associated with Plasmodium falciparum malaria; the sporadic variant is the most common subtype in the rest of the world.⁴

Burkitt lymphoma is highly aggressive and is characterized by unusually high rates of mitosis and apoptosis that result in abundant cellular debris and a distinctive starry-sky pattern on histopathology.^5,6 Extranodal metastasis is common,⁷ but cutaneous involvement is exceedingly rare, with only a few cases having been reported.^8-14 Cutaneous metastasis of Burkitt lymphoma often is associated with a high overall disease burden and poor prognosis.^8,11

Immunodeficiency-related Burkitt lymphoma is particularly aggressive. Notably, 3 of 7 (42.9%) reported cases of cutaneous Burkitt lymphoma occurred in HIV-positive patients.^11,13 In one case, cutaneous involvement was the first sign of relapsed disease that had been in remission.¹²

Although c-MYC rearrangement is required to make a diagnosis of Burkitt lymphoma, the disease also is present in a minority of cases of diffuse large B-cell lymphoma (DLBCL)(6%).¹⁵ Although DLBCL typically can be differentiated from Burkitt lymphoma by the large nuclear size and characteristic vesicular nuclei of B cells, few cases of DLBCL with c-MYC rearrangement histologically mimic Burkitt lymphoma. However, key features such as immunohistochemical staining for Bcl-2 and CD10 can be used to distinguish these 2 entities.¹⁶ Bcl-2 negativity and CD10 positivity, as seen in our patient, is considered more characteristic of Burkitt lymphoma. This staining pattern in combination with a high Ki-67 fraction (>95%) and the presence of monomorphic medium-sized cells is more consistent with a diagnosis of Burkitt lymphoma than of DLBCL.¹⁷

Earlier case reports have documented that cutaneous lesions of Burkitt lymphoma can occur in a variety of ways. Hematogenous spread is the likely route of metastasis for lesions distant to the primary site or those that have widespread distribution.¹⁸ Alternatively, other reports have suggested that cutaneous metastases can occur from local invasion and subcutaneous extension of malignant cells after a surgical procedure.^10,19 For example, cutaneous Burkitt lymphoma has been reported in the setting of celioscopy, occurring directly at the surgical site.¹⁹ In our patient, we believe that the route of metastatic spread likely was through subcutaneous invasion secondary to CT-guided core biopsy, which was supported by the observation that the onset of cutaneous manifestations was temporally related to the procedure and that the lesions occurred on the skin directly overlying the biopsy site.

In conclusion, we describe an exceedingly rare presentation of cutaneous Burkitt lymphoma in which a surgical procedure likely served as an inciting event that triggered seeding of malignant cells to the skin. Cutaneous spread of Burkitt lymphoma is infrequently reported; all such reports that provide long-term follow-up data have described it in association with high disease burden and often a lethal outcome.^8,11,12 Our patient had complete resolution of cutaneous lesions with chemotherapy. It is unclear if the presence of cutaneous lesions can serve as a prognostic indicator and requires further investigation. However, our case provides preliminary evidence to suggest that cutaneous metastases do not always represent aggressive disease and that cutaneous lesions may respond well to chemotherapy.

To the Editor:

A 73-year-old man was admitted to the hospital with progressive abdominal and hip pain of several weeks’ duration that was accompanied by unilateral swelling of the left leg. He had a medical history of hypertension, hyperlipidemia, and prediabetes. Computed tomography (CT) showed extensive intra-abdominal, retroperitoneal, and pelvic lymphadenopathy in addition to poorly defined hepatic lesions.

A CT-guided core biopsy of a left inguinal lymph node showed Burkitt lymphoma. Fluorescence in situ hybridization was positive for oncogene c-MYC rearrangement on chromosome 8q24 and negative for B-cell lymphoma 2 (BCL2) and B-cell lymphoma 6 (BCL6) gene rearrangements. Flow cytometry demonstrated an aberrant population of κ light chain-restricted CD5⁻CD10⁺ B lymphocytes.

The patient’s overall disease burden was consistent with stage IV Burkitt lymphoma. R-miniCHOP chemotherapy—rituximab plus a reduced dose of cyclophosphamide, doxorubicin, vincristine sulfate, and prednisone—was initiated. Approximately 2 weeks after chemotherapy was initiated, the patient developed a firm erythematous eruption on the left hip (Figure 1A). His regimen was then switched to R-EPOCH—rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin—at the time of discharge, and he was referred to dermatology due to an initial concern of an adverse reaction to R-EPOCH chemotherapy. The patient denied any pain, pruritus, or irritation. Physical examination showed multifocal, subcutaneous, indurated, erythematous and violaceous nodules without epidermal changes. Some nodules on the lateral aspect of the hip coalesced to form firm plaques.

A punch biopsy specimen showed markedly atypical lymphocytes with enlarged nuclei and scant cytoplasm present throughout the dermis (Figures 2A and 2B). Numerous apoptotic cells and cellular debris were seen. Immunohistochemical staining demonstrated that the lymphocytic infiltrate comprised CD79a⁺ B cells that were positive for Bcl-6 and CD10 and negative for Bcl-2 (Figures 2C and 2D). There also was diminished focal expression of CD20. Ki-67 protein staining was intensely positive and demonstrated a very high proliferative index.

Taken together, these findings were consistent with a diagnosis of cutaneous metastasis of Burkitt lymphoma. The patient’s cutaneous lesions improved after continued aggressive chemotherapy. At follow-up 2 weeks after biopsy, he was receiving his second round of R-EPOCH chemotherapy with appreciable regression of skin lesions (Figure 1B). However, he then developed right-side double vision, ptosis, and right-side facial paresthesia. Although magnetic resonance imaging of the brain and lumbar puncture did not show evidence of central nervous system involvement, the chemotherapy regimen was switched to dose-adjusted CVAD-R—hypercyclophosphamide, vincristine, doxorubicin hydrochloride, and dexamethasone plus rituximab—for empiric treatment of central nervous system disease. Although treatment was complicated by sepsis with extended-spectrum β-lactamase-producing Enterobacter cloacae, Burkitt lymphoma was found to be in remission after 3 cycles of CVAD-R and 5 months of chemotherapy.

Burkitt lymphoma is a B-cell non-Hodgkin malignancy caused by translocation of chromosome 8 and chromosome 14, leading to overexpression of c-MYC and subsequent hyperproliferation of B lymphocytes.^1,2 The disease is divided into 3 major categories: sporadic, endemic, and immunodeficiency related.³ The endemic variant is the most prevalent subtype in Africa and is associated with Plasmodium falciparum malaria; the sporadic variant is the most common subtype in the rest of the world.⁴

Burkitt lymphoma is highly aggressive and is characterized by unusually high rates of mitosis and apoptosis that result in abundant cellular debris and a distinctive starry-sky pattern on histopathology.^5,6 Extranodal metastasis is common,⁷ but cutaneous involvement is exceedingly rare, with only a few cases having been reported.^8-14 Cutaneous metastasis of Burkitt lymphoma often is associated with a high overall disease burden and poor prognosis.^8,11

Immunodeficiency-related Burkitt lymphoma is particularly aggressive. Notably, 3 of 7 (42.9%) reported cases of cutaneous Burkitt lymphoma occurred in HIV-positive patients.^11,13 In one case, cutaneous involvement was the first sign of relapsed disease that had been in remission.¹²

Although c-MYC rearrangement is required to make a diagnosis of Burkitt lymphoma, the disease also is present in a minority of cases of diffuse large B-cell lymphoma (DLBCL)(6%).¹⁵ Although DLBCL typically can be differentiated from Burkitt lymphoma by the large nuclear size and characteristic vesicular nuclei of B cells, few cases of DLBCL with c-MYC rearrangement histologically mimic Burkitt lymphoma. However, key features such as immunohistochemical staining for Bcl-2 and CD10 can be used to distinguish these 2 entities.¹⁶ Bcl-2 negativity and CD10 positivity, as seen in our patient, is considered more characteristic of Burkitt lymphoma. This staining pattern in combination with a high Ki-67 fraction (>95%) and the presence of monomorphic medium-sized cells is more consistent with a diagnosis of Burkitt lymphoma than of DLBCL.¹⁷

Earlier case reports have documented that cutaneous lesions of Burkitt lymphoma can occur in a variety of ways. Hematogenous spread is the likely route of metastasis for lesions distant to the primary site or those that have widespread distribution.¹⁸ Alternatively, other reports have suggested that cutaneous metastases can occur from local invasion and subcutaneous extension of malignant cells after a surgical procedure.^10,19 For example, cutaneous Burkitt lymphoma has been reported in the setting of celioscopy, occurring directly at the surgical site.¹⁹ In our patient, we believe that the route of metastatic spread likely was through subcutaneous invasion secondary to CT-guided core biopsy, which was supported by the observation that the onset of cutaneous manifestations was temporally related to the procedure and that the lesions occurred on the skin directly overlying the biopsy site.

In conclusion, we describe an exceedingly rare presentation of cutaneous Burkitt lymphoma in which a surgical procedure likely served as an inciting event that triggered seeding of malignant cells to the skin. Cutaneous spread of Burkitt lymphoma is infrequently reported; all such reports that provide long-term follow-up data have described it in association with high disease burden and often a lethal outcome.^8,11,12 Our patient had complete resolution of cutaneous lesions with chemotherapy. It is unclear if the presence of cutaneous lesions can serve as a prognostic indicator and requires further investigation. However, our case provides preliminary evidence to suggest that cutaneous metastases do not always represent aggressive disease and that cutaneous lesions may respond well to chemotherapy.

To the Editor:

Testosterone-replacement therapy (TRT) is indicated for hypogonadism. The benefits of TRT are well documented, with multiple options available for delivery. Testosterone pellet implantation (TPI) is an effective treatment option for hypogonadism with minimal adverse reactions. Availability of TRT is increasing, as facilities are offering off-label applications. Although TPI generally is well tolerated, cutaneous reactions have been documented. We present a patient with drug-induced dermatitis following TPI.

A 51-year-old man with hypogonadism presented with an extremely pruritic rash that began on the left buttock 3 days after receiving his fourth TPI. The patient had received subcutaneous insertions of 8 testosterone pellets (75 mg per pellet every 6 months) to the left buttock. He denied any history of a similar rash. His medical history was remarkable for hyperlipidemia, which was controlled with niacin and omega-3 fatty acids (fish oil). Other medications included glucosamine. Before presenting to our clinic, he was given a 40-mg intramuscular injection of triamcinolone acetonide and trimethoprim-sulfamethoxazole twice daily for 7 days, a methylprednisolone dose pack, and triamcinolone ointment 0.1% twice daily by his primary care physician, all without improvement of the rash.

Physical examination revealed multiple well-circumscribed, coalescing clusters of darkly erythematous papules and dermal plaques of varying size on the buttocks with extension to the lower back, abdomen, and thighs (Figure 1). The differential diagnosis included lichenoid eruption, pseudolymphoma, sarcoidosis, and granuloma annulare.

Testosterone-replacement therapy is becoming more widely available. Lack of regulation of proper marketing by such facilities as medical spas that offer TPI for off-label applications has led to a rampant increase in TRT prescribing, possibly foreshadowing an increase in adverse cutaneous reactions to TRT.⁶

Our case of histologically consistent testosterone pellet–induced dermatitis highlights a rare cutaneous adverse reaction that can occur subsequent to TPI and illustrates the efficacy of high-dose oral steroids as a treatment option. With increased use of TRT, physicians should be cognizant of the potential adverse cutaneous effects related to this treatment and counsel patients appropriately prior to initiating treatment.

Acknowledgment
We thank the patient for granting permission to publish this case.

To the Editor:

Testosterone-replacement therapy (TRT) is indicated for hypogonadism. The benefits of TRT are well documented, with multiple options available for delivery. Testosterone pellet implantation (TPI) is an effective treatment option for hypogonadism with minimal adverse reactions. Availability of TRT is increasing, as facilities are offering off-label applications. Although TPI generally is well tolerated, cutaneous reactions have been documented. We present a patient with drug-induced dermatitis following TPI.

A 51-year-old man with hypogonadism presented with an extremely pruritic rash that began on the left buttock 3 days after receiving his fourth TPI. The patient had received subcutaneous insertions of 8 testosterone pellets (75 mg per pellet every 6 months) to the left buttock. He denied any history of a similar rash. His medical history was remarkable for hyperlipidemia, which was controlled with niacin and omega-3 fatty acids (fish oil). Other medications included glucosamine. Before presenting to our clinic, he was given a 40-mg intramuscular injection of triamcinolone acetonide and trimethoprim-sulfamethoxazole twice daily for 7 days, a methylprednisolone dose pack, and triamcinolone ointment 0.1% twice daily by his primary care physician, all without improvement of the rash.

Physical examination revealed multiple well-circumscribed, coalescing clusters of darkly erythematous papules and dermal plaques of varying size on the buttocks with extension to the lower back, abdomen, and thighs (Figure 1). The differential diagnosis included lichenoid eruption, pseudolymphoma, sarcoidosis, and granuloma annulare.

Testosterone-replacement therapy is becoming more widely available. Lack of regulation of proper marketing by such facilities as medical spas that offer TPI for off-label applications has led to a rampant increase in TRT prescribing, possibly foreshadowing an increase in adverse cutaneous reactions to TRT.⁶

Our case of histologically consistent testosterone pellet–induced dermatitis highlights a rare cutaneous adverse reaction that can occur subsequent to TPI and illustrates the efficacy of high-dose oral steroids as a treatment option. With increased use of TRT, physicians should be cognizant of the potential adverse cutaneous effects related to this treatment and counsel patients appropriately prior to initiating treatment.

Acknowledgment
We thank the patient for granting permission to publish this case.

To the Editor:

Testosterone-replacement therapy (TRT) is indicated for hypogonadism. The benefits of TRT are well documented, with multiple options available for delivery. Testosterone pellet implantation (TPI) is an effective treatment option for hypogonadism with minimal adverse reactions. Availability of TRT is increasing, as facilities are offering off-label applications. Although TPI generally is well tolerated, cutaneous reactions have been documented. We present a patient with drug-induced dermatitis following TPI.

A 51-year-old man with hypogonadism presented with an extremely pruritic rash that began on the left buttock 3 days after receiving his fourth TPI. The patient had received subcutaneous insertions of 8 testosterone pellets (75 mg per pellet every 6 months) to the left buttock. He denied any history of a similar rash. His medical history was remarkable for hyperlipidemia, which was controlled with niacin and omega-3 fatty acids (fish oil). Other medications included glucosamine. Before presenting to our clinic, he was given a 40-mg intramuscular injection of triamcinolone acetonide and trimethoprim-sulfamethoxazole twice daily for 7 days, a methylprednisolone dose pack, and triamcinolone ointment 0.1% twice daily by his primary care physician, all without improvement of the rash.

Physical examination revealed multiple well-circumscribed, coalescing clusters of darkly erythematous papules and dermal plaques of varying size on the buttocks with extension to the lower back, abdomen, and thighs (Figure 1). The differential diagnosis included lichenoid eruption, pseudolymphoma, sarcoidosis, and granuloma annulare.

Testosterone-replacement therapy is becoming more widely available. Lack of regulation of proper marketing by such facilities as medical spas that offer TPI for off-label applications has led to a rampant increase in TRT prescribing, possibly foreshadowing an increase in adverse cutaneous reactions to TRT.⁶

Our case of histologically consistent testosterone pellet–induced dermatitis highlights a rare cutaneous adverse reaction that can occur subsequent to TPI and illustrates the efficacy of high-dose oral steroids as a treatment option. With increased use of TRT, physicians should be cognizant of the potential adverse cutaneous effects related to this treatment and counsel patients appropriately prior to initiating treatment.

Acknowledgment
We thank the patient for granting permission to publish this case.

To the Editor:

Purpura fulminans is a severe and rapidly fatal thrombotic disorder that can occur in association with either hereditary or acquired deficiencies of the natural anticoagulants protein C and protein S.¹ It most commonly results from the acute inflammatory response and subsequent disseminated intravascular coagulation (DIC) seen in severe bacterial septicemia. Excessive bleeding, retiform purpura, and skin necrosis may develop as a result of the coagulopathies of typical DIC.¹Neisseria meningitidis, Streptococcus, and Staphylococcus frequently are implicated as pathogens, but Escherichia coli–associated purpura fulminans in adults is rare.^2,3 We report a case of purpura fulminans in the setting of E coli septicemia.

A 62-year-old woman with a history of end-stage liver disease secondary to alcoholic liver cirrhosis diagnosed 13 years prior complicated by ascites and esophageal varices presented to a primary care clinic for evaluation of a recent-onset nontender lesion on the left buttock. She was hypotensive with a blood pressure of 62/48 mmHg. The patient was prescribed ciprofloxacin 250 mg twice daily and hydrocodone/acetominophen 5 mg/325 mg twice daily as needed for pain management and was discharged. Six hours later, the patient presented to the emergency department with new onset symptoms of confusion and dark-colored spots on the abdomen and lower legs, which her family members noted had developed shortly after the patient took ciprofloxacin. In the emergency department, the patient was noted to be hypotensive and febrile with a severe metabolic acidosis. She was intubated for respiratory failure and received intravenous fluid resuscitation, broad-spectrum antibiotics, and vasopressors. Blood cultures were obtained, and the dermatology department was consulted.

On physical examination, extensive purpuric, reticulated, and stellate plaques with central necrosis and hemorrhagic bullae were noted on the abdomen (Figure, A) and bilateral lower legs (Figure, B) extending onto the thighs. The patient was coagulopathic with persistent sanguineous oozing at intravenous sites and bilateral nares. A small erythematous ulcer with overlying black eschar was noted on the left medial buttock.

Laboratory test results showed new-onset thrombocytopenia, prolonged prothrombin time/international normalized ratio and partial thromboplastin time, and low fibrinogen levels, which confirmed a diagnosis of acute DIC. Blood cultures were positive for gram-negative rods in 4 out of 4 bottles within 12 hours of being drawn. Further testing identified the microorganism as E coli, and antibiotic susceptibility testing revealed it was sensitive to most antibiotics.

The patient was clinically diagnosed with purpura fulminans secondary to severe E coli septicemia and DIC. This life-threatening disorder is considered a medical emergency with a high mortality rate. Laboratory findings supporting DIC include the presence of schistocytes on a peripheral blood smear, thrombocytopenia, positive plasma protamine paracoagulation test, low fibrinogen levels, and positive fibrin degradation products. Reported cases of purpura fulminans in the setting of E coli septicemia are rare, and meningococcemia is the most common presentation.^2,3 Bacterial components (eg, lipopolysaccharides found in the cell walls of gram-negative bacteria) may contribute to the progression of septicemia. Increased levels of endotoxin lipopolysaccharide can lead to septic shock and organ dysfunction.⁴ However, the release of lipooligosaccharides is associated with the development of meningococcal septicemia, and the lipopolysaccharide levels are directly correlated with prognosis in patients without meningitis.^5-7

Human activated protein C concentrate (and its precursor, protein C concentrate) replacement therapy has been shown to improve outcomes in patients with meningococcemia-associated–purpura fulminans and severe sepsis, respectively.⁸ Heparin may be considered in the treatment of patients with purpura fulminans in addition to the replacement of any missing clotting factors or blood products.⁹ The international guidelines for the management of severe sepsis and septic shock include early quantitative resuscitation of the patient during the first 6 hours after recognition of sepsis, performing blood cultures before antibiotic therapy, and administering broad-spectrum antimicrobial therapy within 1 hour of recognition of septic shock.¹⁰ The elapsed time from triage to the actual administration of appropriate antimicrobials are primary determinants of patient mortality.¹¹ Therefore, physicians must act quickly to stabilize the patient.

Gram-positive bacteria and gram-negative diplococci are common infectious agents implicated in purpura fulminans. Escherichia coli rarely has been identified as the inciting agent for purpura fulminans in adults. The increasing frequency of E coli strains that produce extended-spectrum β-lactamases—enzymes that mediate resistance to extended-spectrum (third generation) cephalosporins (eg, ceftazidime, cefotaxime, ceftriaxone) and monobactams (eg, aztreonam)—complicates matters further when deciding on appropriate antibiotics. Patients who have infections from extended-spectrum β-lactamase strains will require more potent carbapenems (eg, meropenem, imipenem) for treatment of infections. Despite undergoing treatment for septicemia, our patient went into cardiac arrest within 24 hours of presentation to the emergency department and died a few hours later. Physicians should consider E coli as an inciting agent of purpura fulminans and consider appropriate empiric antibiotics with gram-negative coverage to include E coli.

To the Editor:

Purpura fulminans is a severe and rapidly fatal thrombotic disorder that can occur in association with either hereditary or acquired deficiencies of the natural anticoagulants protein C and protein S.¹ It most commonly results from the acute inflammatory response and subsequent disseminated intravascular coagulation (DIC) seen in severe bacterial septicemia. Excessive bleeding, retiform purpura, and skin necrosis may develop as a result of the coagulopathies of typical DIC.¹Neisseria meningitidis, Streptococcus, and Staphylococcus frequently are implicated as pathogens, but Escherichia coli–associated purpura fulminans in adults is rare.^2,3 We report a case of purpura fulminans in the setting of E coli septicemia.

A 62-year-old woman with a history of end-stage liver disease secondary to alcoholic liver cirrhosis diagnosed 13 years prior complicated by ascites and esophageal varices presented to a primary care clinic for evaluation of a recent-onset nontender lesion on the left buttock. She was hypotensive with a blood pressure of 62/48 mmHg. The patient was prescribed ciprofloxacin 250 mg twice daily and hydrocodone/acetominophen 5 mg/325 mg twice daily as needed for pain management and was discharged. Six hours later, the patient presented to the emergency department with new onset symptoms of confusion and dark-colored spots on the abdomen and lower legs, which her family members noted had developed shortly after the patient took ciprofloxacin. In the emergency department, the patient was noted to be hypotensive and febrile with a severe metabolic acidosis. She was intubated for respiratory failure and received intravenous fluid resuscitation, broad-spectrum antibiotics, and vasopressors. Blood cultures were obtained, and the dermatology department was consulted.

On physical examination, extensive purpuric, reticulated, and stellate plaques with central necrosis and hemorrhagic bullae were noted on the abdomen (Figure, A) and bilateral lower legs (Figure, B) extending onto the thighs. The patient was coagulopathic with persistent sanguineous oozing at intravenous sites and bilateral nares. A small erythematous ulcer with overlying black eschar was noted on the left medial buttock.

Laboratory test results showed new-onset thrombocytopenia, prolonged prothrombin time/international normalized ratio and partial thromboplastin time, and low fibrinogen levels, which confirmed a diagnosis of acute DIC. Blood cultures were positive for gram-negative rods in 4 out of 4 bottles within 12 hours of being drawn. Further testing identified the microorganism as E coli, and antibiotic susceptibility testing revealed it was sensitive to most antibiotics.

The patient was clinically diagnosed with purpura fulminans secondary to severe E coli septicemia and DIC. This life-threatening disorder is considered a medical emergency with a high mortality rate. Laboratory findings supporting DIC include the presence of schistocytes on a peripheral blood smear, thrombocytopenia, positive plasma protamine paracoagulation test, low fibrinogen levels, and positive fibrin degradation products. Reported cases of purpura fulminans in the setting of E coli septicemia are rare, and meningococcemia is the most common presentation.^2,3 Bacterial components (eg, lipopolysaccharides found in the cell walls of gram-negative bacteria) may contribute to the progression of septicemia. Increased levels of endotoxin lipopolysaccharide can lead to septic shock and organ dysfunction.⁴ However, the release of lipooligosaccharides is associated with the development of meningococcal septicemia, and the lipopolysaccharide levels are directly correlated with prognosis in patients without meningitis.^5-7

Human activated protein C concentrate (and its precursor, protein C concentrate) replacement therapy has been shown to improve outcomes in patients with meningococcemia-associated–purpura fulminans and severe sepsis, respectively.⁸ Heparin may be considered in the treatment of patients with purpura fulminans in addition to the replacement of any missing clotting factors or blood products.⁹ The international guidelines for the management of severe sepsis and septic shock include early quantitative resuscitation of the patient during the first 6 hours after recognition of sepsis, performing blood cultures before antibiotic therapy, and administering broad-spectrum antimicrobial therapy within 1 hour of recognition of septic shock.¹⁰ The elapsed time from triage to the actual administration of appropriate antimicrobials are primary determinants of patient mortality.¹¹ Therefore, physicians must act quickly to stabilize the patient.

Gram-positive bacteria and gram-negative diplococci are common infectious agents implicated in purpura fulminans. Escherichia coli rarely has been identified as the inciting agent for purpura fulminans in adults. The increasing frequency of E coli strains that produce extended-spectrum β-lactamases—enzymes that mediate resistance to extended-spectrum (third generation) cephalosporins (eg, ceftazidime, cefotaxime, ceftriaxone) and monobactams (eg, aztreonam)—complicates matters further when deciding on appropriate antibiotics. Patients who have infections from extended-spectrum β-lactamase strains will require more potent carbapenems (eg, meropenem, imipenem) for treatment of infections. Despite undergoing treatment for septicemia, our patient went into cardiac arrest within 24 hours of presentation to the emergency department and died a few hours later. Physicians should consider E coli as an inciting agent of purpura fulminans and consider appropriate empiric antibiotics with gram-negative coverage to include E coli.

To the Editor:

Purpura fulminans is a severe and rapidly fatal thrombotic disorder that can occur in association with either hereditary or acquired deficiencies of the natural anticoagulants protein C and protein S.¹ It most commonly results from the acute inflammatory response and subsequent disseminated intravascular coagulation (DIC) seen in severe bacterial septicemia. Excessive bleeding, retiform purpura, and skin necrosis may develop as a result of the coagulopathies of typical DIC.¹Neisseria meningitidis, Streptococcus, and Staphylococcus frequently are implicated as pathogens, but Escherichia coli–associated purpura fulminans in adults is rare.^2,3 We report a case of purpura fulminans in the setting of E coli septicemia.

A 62-year-old woman with a history of end-stage liver disease secondary to alcoholic liver cirrhosis diagnosed 13 years prior complicated by ascites and esophageal varices presented to a primary care clinic for evaluation of a recent-onset nontender lesion on the left buttock. She was hypotensive with a blood pressure of 62/48 mmHg. The patient was prescribed ciprofloxacin 250 mg twice daily and hydrocodone/acetominophen 5 mg/325 mg twice daily as needed for pain management and was discharged. Six hours later, the patient presented to the emergency department with new onset symptoms of confusion and dark-colored spots on the abdomen and lower legs, which her family members noted had developed shortly after the patient took ciprofloxacin. In the emergency department, the patient was noted to be hypotensive and febrile with a severe metabolic acidosis. She was intubated for respiratory failure and received intravenous fluid resuscitation, broad-spectrum antibiotics, and vasopressors. Blood cultures were obtained, and the dermatology department was consulted.

On physical examination, extensive purpuric, reticulated, and stellate plaques with central necrosis and hemorrhagic bullae were noted on the abdomen (Figure, A) and bilateral lower legs (Figure, B) extending onto the thighs. The patient was coagulopathic with persistent sanguineous oozing at intravenous sites and bilateral nares. A small erythematous ulcer with overlying black eschar was noted on the left medial buttock.

Laboratory test results showed new-onset thrombocytopenia, prolonged prothrombin time/international normalized ratio and partial thromboplastin time, and low fibrinogen levels, which confirmed a diagnosis of acute DIC. Blood cultures were positive for gram-negative rods in 4 out of 4 bottles within 12 hours of being drawn. Further testing identified the microorganism as E coli, and antibiotic susceptibility testing revealed it was sensitive to most antibiotics.

The patient was clinically diagnosed with purpura fulminans secondary to severe E coli septicemia and DIC. This life-threatening disorder is considered a medical emergency with a high mortality rate. Laboratory findings supporting DIC include the presence of schistocytes on a peripheral blood smear, thrombocytopenia, positive plasma protamine paracoagulation test, low fibrinogen levels, and positive fibrin degradation products. Reported cases of purpura fulminans in the setting of E coli septicemia are rare, and meningococcemia is the most common presentation.^2,3 Bacterial components (eg, lipopolysaccharides found in the cell walls of gram-negative bacteria) may contribute to the progression of septicemia. Increased levels of endotoxin lipopolysaccharide can lead to septic shock and organ dysfunction.⁴ However, the release of lipooligosaccharides is associated with the development of meningococcal septicemia, and the lipopolysaccharide levels are directly correlated with prognosis in patients without meningitis.^5-7

Human activated protein C concentrate (and its precursor, protein C concentrate) replacement therapy has been shown to improve outcomes in patients with meningococcemia-associated–purpura fulminans and severe sepsis, respectively.⁸ Heparin may be considered in the treatment of patients with purpura fulminans in addition to the replacement of any missing clotting factors or blood products.⁹ The international guidelines for the management of severe sepsis and septic shock include early quantitative resuscitation of the patient during the first 6 hours after recognition of sepsis, performing blood cultures before antibiotic therapy, and administering broad-spectrum antimicrobial therapy within 1 hour of recognition of septic shock.¹⁰ The elapsed time from triage to the actual administration of appropriate antimicrobials are primary determinants of patient mortality.¹¹ Therefore, physicians must act quickly to stabilize the patient.

Gram-positive bacteria and gram-negative diplococci are common infectious agents implicated in purpura fulminans. Escherichia coli rarely has been identified as the inciting agent for purpura fulminans in adults. The increasing frequency of E coli strains that produce extended-spectrum β-lactamases—enzymes that mediate resistance to extended-spectrum (third generation) cephalosporins (eg, ceftazidime, cefotaxime, ceftriaxone) and monobactams (eg, aztreonam)—complicates matters further when deciding on appropriate antibiotics. Patients who have infections from extended-spectrum β-lactamase strains will require more potent carbapenems (eg, meropenem, imipenem) for treatment of infections. Despite undergoing treatment for septicemia, our patient went into cardiac arrest within 24 hours of presentation to the emergency department and died a few hours later. Physicians should consider E coli as an inciting agent of purpura fulminans and consider appropriate empiric antibiotics with gram-negative coverage to include E coli.