- Email: [email protected]
Out of the frying pan and into the fire
1816
993
Enoxaparin-induced bullous hemorrhagic dermatosis Ryan Andrulonis, MD, Geisinger Medical Center, Danville, PA, United States; Victor Marks, MD, Geisinger Medical Center, Danville, PA, United States Background: Enoxaparin is a low molecular weight heparin (LMWH). LMWH and unfractionated heparin (UFH) are used frequently for anticoagulation by activating antithrombin III. Numerous adverse skin reactions have been reported with the use of LMWH and UFH. Recently, bullous hemorrhagic dermatosis associated with the use of LMWH and UFH has been reported. Case report: An 87-year-old woman was admitted to the hospital for management of a recurrent chylothorax. She had a history of pulmonary embolism and was on chronic warfarin therapy which was held for 5 days before hospitalization. Enoxaparin was initiated on admission. Ten days after enoxaparin was started, the patient developed asymptomatic hemorrhagic bullae overlying her knees, forearms, and elbows. A biopsy was obtained from a lesion on the right elbow revealing a subepidermal vesicle with blood and fibrin and underlying hemorrhage. No vasculitis, vasculopathy, or findings suggestive of a primary autoimmune bullous disorder were identified. Laboratory evaluation revealed a normal LMWH level and a mild thrombocytopenia which was higher than her platelet count measured on admission. The day following the biopsy, the patient was transferred to another facility. Subsequent management of her anticoagulation was unknown. Two weeks later, the patient reported that her bullae were resolving. Discussion: Bullous hemorrhagic dermatosis associated with UFH and LMWH is a recently described entity. This typically occurs in elderly, male patients. Distinctively, the bullae in this condition appear at locations distant from the medication injection sites, often involving the extremities, and develop between one day and one month after the offending agent is started. Biopsy typically shows subcorneal or intraepidermal blood filled bullae, although subepidermal bullae have been reported. There can be dermal inflammation, but vasculitis and vasculopathy are absent and direct immunofluorescence is negative. The mechanism underlying this condition is unknown. Optimal therapy has not been defined, but resolution of the bullae may occur despite continued use of UFH or LMWH.
Case report: The mistaken identity of S100 protein Seow Hoong Foo, MBBS, Sandwell and West Birmingham Hospitals Trust, Birmingham, United Kingdom; Madhavi Maheshwri, MBBS, Sandwell and West Birmingham Hospitals Trust, Birmingham, United Kingdom; Kim Varma, MBBS, Sandwell and West Birmingham Hospitals Trust, Birmingham, United Kingdom; Agustin Martin-Clavijo, MBBS, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom; Rahul Hejmadi, MBBS, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom S100 protein is one of the commonest antibodies used to confirm metastatic melanoma. In addition, it is also normally expressed in various other cells including neural tissues, chondrocytes, Langerhans cells, dendritic cells and keratinocytes. We would like to report a case where dependence of S100 protein immunohistochemistry as a marker of metastatic melanoma led to a wrong diagnosis. A 43-year-old man presented with a changing mole on his back. Histology report of excision confirmed melanoma in situ. This was further treated with wide local excision. During his follow-up appointment, he was found to have 1 new asymptomatic left cervical lymph node. An urgent staging computer tomography (CT) scan revealed multiple small ill-defined lung nodules diffusely scattered throughout both lungs with relative sparing of the lung bases. Patient had an initial bronchoscopy which was negative. Patient proceeded to have video-assisted thoracotomy (VAT) lung wedge biopsy. Hematoxylineeosin sections from the lung biopsy showed aggregates of elongated monomorphic epithelioid cells with nuclear longitudinal grooves. On immunohistochemistry, these cells were S100 proteinepositive. This was thought to be in keeping with a diagnosis of metastatic melanoma in a patient with a history of melanoma. Patient was then referred to the Regional Specialist Skin Cancer MultiDisciplinary Team for further management of metastatic melanoma. The lung wedge biopsy was reexamined and in view of the characteristic morphologic appearance, the possibility of these representing Langerhans cells was strongly suspected. Immunohistochemistry for CD1a was requested which was strongly positive. This confirmed Langerhans cell histiocytosis (LCH). Patient was referred to the Hematology team for management of his LCH. He responded well to methotrexate 10 mg once a week in combination with prednisolone 20 mg once a day. In conclusion, we presented a case of pulmonary LCH which was misdiagnosed as stage 4 metastatic melanoma; 2 entities with very different prognostic outcomes. Stage 4 melanoma has a 5-year survival rate of about 15% to 20%. Pulmonary LCH is thought to be an essentially reactive condition, and approximately 50% of patients have complete resolution. This case highlights the importance of a multidisciplinary team approach to management of difficult cases and to remind ourselves that S100 protein can be expressed in a diverse spectrum of tissues, not just in melanoma.
Conclusion: Bullous hemorrhagic dermatosis related to UFH and LMWH use may be underreported, as this may resolve spontaneously. Further investigation is required to determine the etiology and optimal therapy. Commercial support: None identified.
Commercial support: None identified.
536 Cutaneous melioidosis with unusual histologic features Benson Yeo, MBBS, National Skin Centre, Singapore; Joyce Lee, MBBS, National Skin Centre, Singapore; Uma Alagappan, MBBS, Changi General Hospital, Singapore; Jiun Yit Pan, MBBS, National Skin Centre, Singapore Background: Melioidosis is an infection caused by the Gram-negative bacillus Burkholderia pseudomallei and is endemic in Northern Australia and many Southeast Asian countries. Humans are mostly infected after contact with soil. The histology of human melioidosis usually shows acute to chronic granulomatous inflammation. We report a case of primary cutaneous melioidosis in a young man with military exposure and unusual histology. Case report: Our patient is a healthy 28-year-old Chinese man with no medical history. He presented with a 1-year history of slowly enlarging ulcer on his left knee which started after scraping it during military outfield training. Examination showed a 5.7 cm 3 3.7 cm ulcerated plaque on his left knee with seropurulent discharge. Patient was systemically well and afebrile, with no clinical evidence of disseminated infection. Investigations including full blood count, renal panel, liver function test, and a chest radiograph were normal. A left knee radiograph did not show underlying osteomyelitis. A skin biopsy showed psoriasiform hyperplasia with dense lymphoplasmacytic dermal infiltrate. No formed granulomas or Gram-negative bacteria were seen. Tissue culture grew Burkholderia pseudomallei. Our patient failed a trial of oral therapy with 6 weeks of amoxicillin-clavulanic acid, and required admission for 2 weeks of intravenous ceftazidime. He was subsequently discharged with a 3-month course of cotrimoxazole. Discussion: Primary cutaneous involvement accounts for about 13% of melioidosis. Patients with cutaneous melioidosis, like our patient, are usually younger, have less risk factors and better prognosis than those with other forms of melioidosis. Multiple reports of melioidosis in survivors of the 2004 Indian Ocean Tsunami renewed interest in this infection. Previous histopathologic studies of human melioidosis described chronic or suppurative granulomatous inflammation, often with intracellular Gram-negative bacilli within macrophages or giant cells. In contrast, our patient’s histology showed a dense superficial and deep perivascular infiltrate of lymphocytes and numerous plasma cells, with no macrophages or formed granulomas found. This unusual histology may mislead unsuspecting clinicians because of the absence of granulomatous inflammation. The lack of TH1 response with absent granulomas may have contributed to the failure of oral antibiotics in our patient.
Out of the frying pan and into the fire Marie-Louise Lovgren, MBBS, Southern General Hospital, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom; Ian Taggart, MBBS, Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom; David Bilsland, MBBS, Southern General Hospital, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom A 38 year-old male with severe psoriasis was undergoing bath psoralen and ultraviolet A (PUVA) treatment, with acitretin 30 mg OD. Following the third phototherapy session (0.36 J/cm2), on his way home he spent 4 minutes in a highstreet tanning cubicle. The patient’s Dermatology Quality of Life Index (DQLI) was 23 and his aim was to accelerate clearance of psoriasis before a holiday. Unfortunately this was cancelled due to his admission to the Burns Unit. He developed burns to 90% of the body surface area with blistering to the lower limbs. He was managed conservatively and discharged after 3 days; the erythema took 2 weeks to settle. Although milder cases of PUVA erythema are relatively common and are a normal expectation of treatment, there are reports of severe burn injuries induced by PUVA with 1 reported death. These are due to medical errors, patient behavior, and cosmetic psoralen misuse. Phototherapy burns accounted for 1 in 3 dermatology legal claims in Scotland over a 12-year period. In America, phototherapy is the third commonest error reported in dermatology. Hence, comprehensive documentation of phototherapy case notes and patient information provided is essential. It is vital that patients are told to avoid sunbeds when receiving phototherapy. In 2012, 90% of commercial sunbeds in England exceeded UV radiation limits set by British and European standards. Most sunbeds emit significant amounts of UVB and UVA. The review of English tanning beds indicated that the mean skin cancer risk was 2.3 times that of Mediterranean sunlight at noon, and the maximum six times higher. Our case highlights the significant impact psoriasis can have on patients’ social and psychological well-being, and that even with appropriate counselling, patients will occasionally ignore or forget advice.
Commercial support: None identified.
Commercial support: None identified.
AB2
J AM ACAD DERMATOL
1916
MAY 2015
993
Enoxaparin-induced bullous hemorrhagic dermatosis Ryan Andrulonis, MD, Geisinger Medical Center, Danville, PA, United States; Victor Marks, MD, Geisinger Medical Center, Danville, PA, United States Background: Enoxaparin is a low molecular weight heparin (LMWH). LMWH and unfractionated heparin (UFH) are used frequently for anticoagulation by activating antithrombin III. Numerous adverse skin reactions have been reported with the use of LMWH and UFH. Recently, bullous hemorrhagic dermatosis associated with the use of LMWH and UFH has been reported. Case report: An 87-year-old woman was admitted to the hospital for management of a recurrent chylothorax. She had a history of pulmonary embolism and was on chronic warfarin therapy which was held for 5 days before hospitalization. Enoxaparin was initiated on admission. Ten days after enoxaparin was started, the patient developed asymptomatic hemorrhagic bullae overlying her knees, forearms, and elbows. A biopsy was obtained from a lesion on the right elbow revealing a subepidermal vesicle with blood and fibrin and underlying hemorrhage. No vasculitis, vasculopathy, or findings suggestive of a primary autoimmune bullous disorder were identified. Laboratory evaluation revealed a normal LMWH level and a mild thrombocytopenia which was higher than her platelet count measured on admission. The day following the biopsy, the patient was transferred to another facility. Subsequent management of her anticoagulation was unknown. Two weeks later, the patient reported that her bullae were resolving. Discussion: Bullous hemorrhagic dermatosis associated with UFH and LMWH is a recently described entity. This typically occurs in elderly, male patients. Distinctively, the bullae in this condition appear at locations distant from the medication injection sites, often involving the extremities, and develop between one day and one month after the offending agent is started. Biopsy typically shows subcorneal or intraepidermal blood filled bullae, although subepidermal bullae have been reported. There can be dermal inflammation, but vasculitis and vasculopathy are absent and direct immunofluorescence is negative. The mechanism underlying this condition is unknown. Optimal therapy has not been defined, but resolution of the bullae may occur despite continued use of UFH or LMWH.
Case report: The mistaken identity of S100 protein Seow Hoong Foo, MBBS, Sandwell and West Birmingham Hospitals Trust, Birmingham, United Kingdom; Madhavi Maheshwri, MBBS, Sandwell and West Birmingham Hospitals Trust, Birmingham, United Kingdom; Kim Varma, MBBS, Sandwell and West Birmingham Hospitals Trust, Birmingham, United Kingdom; Agustin Martin-Clavijo, MBBS, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom; Rahul Hejmadi, MBBS, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom S100 protein is one of the commonest antibodies used to confirm metastatic melanoma. In addition, it is also normally expressed in various other cells including neural tissues, chondrocytes, Langerhans cells, dendritic cells and keratinocytes. We would like to report a case where dependence of S100 protein immunohistochemistry as a marker of metastatic melanoma led to a wrong diagnosis. A 43-year-old man presented with a changing mole on his back. Histology report of excision confirmed melanoma in situ. This was further treated with wide local excision. During his follow-up appointment, he was found to have 1 new asymptomatic left cervical lymph node. An urgent staging computer tomography (CT) scan revealed multiple small ill-defined lung nodules diffusely scattered throughout both lungs with relative sparing of the lung bases. Patient had an initial bronchoscopy which was negative. Patient proceeded to have video-assisted thoracotomy (VAT) lung wedge biopsy. Hematoxylineeosin sections from the lung biopsy showed aggregates of elongated monomorphic epithelioid cells with nuclear longitudinal grooves. On immunohistochemistry, these cells were S100 proteinepositive. This was thought to be in keeping with a diagnosis of metastatic melanoma in a patient with a history of melanoma. Patient was then referred to the Regional Specialist Skin Cancer MultiDisciplinary Team for further management of metastatic melanoma. The lung wedge biopsy was reexamined and in view of the characteristic morphologic appearance, the possibility of these representing Langerhans cells was strongly suspected. Immunohistochemistry for CD1a was requested which was strongly positive. This confirmed Langerhans cell histiocytosis (LCH). Patient was referred to the Hematology team for management of his LCH. He responded well to methotrexate 10 mg once a week in combination with prednisolone 20 mg once a day. In conclusion, we presented a case of pulmonary LCH which was misdiagnosed as stage 4 metastatic melanoma; 2 entities with very different prognostic outcomes. Stage 4 melanoma has a 5-year survival rate of about 15% to 20%. Pulmonary LCH is thought to be an essentially reactive condition, and approximately 50% of patients have complete resolution. This case highlights the importance of a multidisciplinary team approach to management of difficult cases and to remind ourselves that S100 protein can be expressed in a diverse spectrum of tissues, not just in melanoma.
Conclusion: Bullous hemorrhagic dermatosis related to UFH and LMWH use may be underreported, as this may resolve spontaneously. Further investigation is required to determine the etiology and optimal therapy. Commercial support: None identified.
Commercial support: None identified.
536 Cutaneous melioidosis with unusual histologic features Benson Yeo, MBBS, National Skin Centre, Singapore; Joyce Lee, MBBS, National Skin Centre, Singapore; Uma Alagappan, MBBS, Changi General Hospital, Singapore; Jiun Yit Pan, MBBS, National Skin Centre, Singapore Background: Melioidosis is an infection caused by the Gram-negative bacillus Burkholderia pseudomallei and is endemic in Northern Australia and many Southeast Asian countries. Humans are mostly infected after contact with soil. The histology of human melioidosis usually shows acute to chronic granulomatous inflammation. We report a case of primary cutaneous melioidosis in a young man with military exposure and unusual histology. Case report: Our patient is a healthy 28-year-old Chinese man with no medical history. He presented with a 1-year history of slowly enlarging ulcer on his left knee which started after scraping it during military outfield training. Examination showed a 5.7 cm 3 3.7 cm ulcerated plaque on his left knee with seropurulent discharge. Patient was systemically well and afebrile, with no clinical evidence of disseminated infection. Investigations including full blood count, renal panel, liver function test, and a chest radiograph were normal. A left knee radiograph did not show underlying osteomyelitis. A skin biopsy showed psoriasiform hyperplasia with dense lymphoplasmacytic dermal infiltrate. No formed granulomas or Gram-negative bacteria were seen. Tissue culture grew Burkholderia pseudomallei. Our patient failed a trial of oral therapy with 6 weeks of amoxicillin-clavulanic acid, and required admission for 2 weeks of intravenous ceftazidime. He was subsequently discharged with a 3-month course of cotrimoxazole. Discussion: Primary cutaneous involvement accounts for about 13% of melioidosis. Patients with cutaneous melioidosis, like our patient, are usually younger, have less risk factors and better prognosis than those with other forms of melioidosis. Multiple reports of melioidosis in survivors of the 2004 Indian Ocean Tsunami renewed interest in this infection. Previous histopathologic studies of human melioidosis described chronic or suppurative granulomatous inflammation, often with intracellular Gram-negative bacilli within macrophages or giant cells. In contrast, our patient’s histology showed a dense superficial and deep perivascular infiltrate of lymphocytes and numerous plasma cells, with no macrophages or formed granulomas found. This unusual histology may mislead unsuspecting clinicians because of the absence of granulomatous inflammation. The lack of TH1 response with absent granulomas may have contributed to the failure of oral antibiotics in our patient.
Out of the frying pan and into the fire Marie-Louise Lovgren, MBBS, Southern General Hospital, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom; Ian Taggart, MBBS, Glasgow Royal Infirmary, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom; David Bilsland, MBBS, Southern General Hospital, NHS Greater Glasgow and Clyde, Glasgow, United Kingdom A 38 year-old male with severe psoriasis was undergoing bath psoralen and ultraviolet A (PUVA) treatment, with acitretin 30 mg OD. Following the third phototherapy session (0.36 J/cm2), on his way home he spent 4 minutes in a highstreet tanning cubicle. The patient’s Dermatology Quality of Life Index (DQLI) was 23 and his aim was to accelerate clearance of psoriasis before a holiday. Unfortunately this was cancelled due to his admission to the Burns Unit. He developed burns to 90% of the body surface area with blistering to the lower limbs. He was managed conservatively and discharged after 3 days; the erythema took 2 weeks to settle. Although milder cases of PUVA erythema are relatively common and are a normal expectation of treatment, there are reports of severe burn injuries induced by PUVA with 1 reported death. These are due to medical errors, patient behavior, and cosmetic psoralen misuse. Phototherapy burns accounted for 1 in 3 dermatology legal claims in Scotland over a 12-year period. In America, phototherapy is the third commonest error reported in dermatology. Hence, comprehensive documentation of phototherapy case notes and patient information provided is essential. It is vital that patients are told to avoid sunbeds when receiving phototherapy. In 2012, 90% of commercial sunbeds in England exceeded UV radiation limits set by British and European standards. Most sunbeds emit significant amounts of UVB and UVA. The review of English tanning beds indicated that the mean skin cancer risk was 2.3 times that of Mediterranean sunlight at noon, and the maximum six times higher. Our case highlights the significant impact psoriasis can have on patients’ social and psychological well-being, and that even with appropriate counselling, patients will occasionally ignore or forget advice.
Commercial support: None identified.
Commercial support: None identified.
AB2
J AM ACAD DERMATOL
1916
MAY 2015