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Treatment of toxic epidermal necrolysis with intravenous immunoglobulin: The Washington Hospital Center experience
P2601
P2603
Acrokeratosis neoplastica of Bazex without associated malignancy after 2 years of suggestive cutaneous findings: A case report Miranda Smith, MD, University of Oklahoma Health Science Center, Department of Dermatology, Oklahoma City, OK, United States; Renee Grau, MD, University of Oklahoma Health Science Center, Department of Dermatology, Oklahoma City, OK, United States
Treatment of toxic epidermal necrolysis with intravenous immunoglobulin: The Washington Hospital Center experience Suzanne Meyer, MD, Washington Hospital Center, Washington, DC, United States; Alan Moshell, MD, Washington Hospital Center, Washington, DC, United States; Joseph F. Sobanko, MD, Washington Hospital Center, Washington, DC, United States; Kevin Hogan, MD, Georgetown University Hospital, Washington, DC, United States; Thomas P. Nigra, MD, Washington Hospital Center, Washington, DC, United States Background: Toxic epidermal necrolysis (TEN) is a severe adverse mucocutaneous drug reaction where[30% of the total body surface area (TBSA) of skin sloughs after exposure to an inciting medication. The FaseFasL interaction is believed to play a major role in the etiology of this eruption. The use of intravenous immunoglobulin (IVIG), which has been demonstrated to block Fas-mediated keratinocyte apoptosis, has been reported in numerous case series to be of benefit in patients with TEN. However, there is also evidence to suggest the contrary and as such, the standard use of IVIG in TEN remains controversial.
Acrokeratosis neoplastica of Bazex is a rare condition which has been found to be a distinctive marker of malignancy, specifically supradiaphragmatic neoplasia. The cutaneous findings of this syndrome often precede the diagnosis of malignancy and generally the malignancy is found within months of the onset of the cutaneous manifestations. These cutaneous signs include papulosquamous lesions, hyperpigmentation, keratoderma, paronychia, and nail dystrophy. The classic finding is erythematous to violaceous patches or plaques found symmetrically on acral skin. The majority of patients will have symptomatic improvement with treatment of the underlying malignancy; however, this syndrome is otherwise resistant to treatment. We present a case of apparent Bazex syndrome with extensive work-up for malignancy over the past 2 years which has found no malignancy thus far. In addition to those of Bazex, the patient also has other classic cutaneous paraneoplastic signs including acanthosis nigricans and tripe palms, all of which arose over the preceding 2 years. Commercial support: None identified.
Objective: To perform a retrospective analysis of patients with biopsy-proven TEN treated with IVIG at our institution. Our null hypothesis was that administration of IVIG does not affect the mortality of patients with TEN. Design: A chart review was performed of all patients that carried the diagnosis of StevenseJohnson syndrome (SJS) or TEN from 1999 to 2006. Patients included in the analysis needed to meet the following criteria: [30% TBSA epidermal detachment, administration of IVIG, and histologic confirmation of the diagnosis of TEN. Administration of systemic corticosteroids was permissible in these patients; however, the concomitant use of other systemic therapies suggested to be of benefit in the setting of TEN was a criterion of exclusion. Patients who received IVIG with skin sloughing \30% TBSA (ie, SJS) were also excluded. Various parameters were recorded and analyzed and the SCORTEN was calculated for each patient included in the analysis. To determine whether the use of IVIG caused a significant reduction in mortality, a test of proportions for binomial distribution was performed, comparing expected and observed mortality overall and for each SCORTEN category. The significance level (a) was set at 0.10. Results: Twenty-one patients (12 men, 9 women) with biopsy-proven TEN were treated with cessation of the offending agent, standard wound care and IVIG at 0.4 g/kg/day for 5 consecutive days for a total dose of 2 g/kg. No severe adverse effects were observed as a consequence of IVIG infusion. Four patients died despite treatment with IVIG, resulting in a mortality rate of 19%. However, when the SCORTEN of the included patients in this study was evaluated, the expected mortality rate of our population was 37.2%. When comparing the death frequency of the sample of our 21 TEN patients to the expected death frequency, the overall cumulative probability was calculated to be statistically significant (0.0629). Conclusions: This retrospective analysis demonstrates that IVIG significantly reduced mortality in patients treated for TEN in our institution. It must be noted, however, that the results using a sample size of 21 does not have sufficient power to give conclusive results. It is recommended that a larger sample size be used in a future study to have sufficient power. Commercial support: None identified.
P2604
P2602 Sirolimus-associated lymphedema: Eight new cases Nemesha Desai, MD, St George’s Hospital, Tooting, London, United Kingdom; Peter Mortimer, MD, MBChB, St George’s Hospital, Tooting, London, United Kingdom Sirolimus (or rapamycin) is a mammalian target of rapamycin (mTOR) inhibitor with immunosuppressant and antiproliferative properties. It is licensed for use in the prophylaxis of organ rejection in adult patients who have received renal transplantation. Documented side effects include dyslipidemia, impaired wound healing, and an increase in lymphocoele formation. There are emerging reports of sirolimusassociated lymphedema involving sites local and distant to previous surgery. We report a series of eight new cases. A 57-year-old male presented with a 4-year history of right lower limb lymphedema. His symptoms began 18 months after a right iliac fossa cadaveric renal transplant and 9 months after commencing sirolimus (average dose 2 mg od). He had a history of end-stage renal failure secondary to congenital hydronephrosis and reflux, two failed renal transplants and an idiopathic hydrocoele. There was no family history of lymphedema. Imaging of the renal tract and right lower limb venous system was normal. Lymphoscintigraphy demonstrated right sided obstruction to lymph flow through the main lower limb lymphatics with rerouting through dermal collaterals. In the absence of other obvious causes, a diagnosis of sirolimus associated lymphedema was made. There was no improvement in lymphedema following drug withdrawal. We have since observed seven further cases of sirolimus associated lymphedema in transplant patients receiving sirolimus for 2 to 10 months before symptom onset. In five cases, the site of lymphedema was anatomically related to previous transplant surgery or hemodialysis access. Two cases had bilateral lymphedema. Lymphoscintigraphy universally showed obstruction to lymphatic flow through the main lymphatic channels. In contrast to the literature, none of our patients improved on drug withdrawal. The mechanism of sirolimus-associated lymphedema is unclear. Vascular endothelial growth factors (VEGF) C and D are known to play a key role in lymphatic proliferation, migration and survival. Recent studies have demonstrated that mTOR is a downstream signal in the VEGF-C pathway, suggesting that sirolimus-induced postsurgical inhibition of lymphangiogenesis and lymphatic survival may contribute to the etiology of clinical lymphedema. Commercial support: None identified.
MARCH 2009
Fulminant myocarditis as a late sequelae of DRESS syndrome Greg P. Bourgeois, University of Alabama at Birmingham, Department of Dermatology, Birmingham, AL, United States; Jennifer A. Cafardi, MD, University of Alabama at Birmingham, Department of Dermatology, Birmingham, AL, United States; Lauren C. Hughey, MD, University of Alabama at Birmingham, Department of Dermatology, Birmingham, AL, United States; Vlada Groysman, MD, University of Alabama at Birmingham, Department of Dermatology, Birmingham, AL, United States Drug rash with eosinophilia and systemic symptoms (DRESS), also known as drug hypersensitivity syndrome, is a severe cutaneous drug reaction that affects numerous organ systems and is associated with a high mortality. This eruption typically results in a rash, facial edema, lymphadenopathy, hepatitis, peripheral eosinophilia, and fever. We report two cases of fulminant myocarditis as a late sequelae of DRESS; each case of DRESS was related to sulfa-containing medications. These patients presented with myocarditis 4 to 6 months after the initial presentation of DRESS with severe chest pain and dyspnea. Both had elevated cardiac enzymes at initial evaluation, and their ventricular ejection fractions rapidly deteriorated. The first patient was a 30-year-old black female who was on both oral prednisone and intravenous immunoglobulin (IVIG) every 6 weeks at the time of presentation as treatment for her refractory, persistent symptoms of DRESS syndrome. She initially presented with a morbilliform eruption that progressed to an exfoliative erythroderma, however, her cutaneous findings were slowly improving at the time of subsequent presentation. The patient described symptoms of increasing dyspnea and acute onset chest pain. Cardiac evaluation in the emergency room revealed STelevation on the electrocardiogram and elevated cardiac enzymes. Cardiac catheterization was performed emergently and showed patent coronary vessels. Pericarditis was noted on echocardiogram, and given elevated enzymes, a myocarditis was suspected. All viral titers were negative making a viral etiology of the myocarditis less likely. The corticosteroid dose was increased during the hospitalization, however, the patient died from refractory arrhythmias. A post-mortem evaluation showed significant eosinophilic infiltration of all layers of the heart as well as complete necrosis of areas of the myocardium. The second patient was a 28-year-old black female, also with an initial morbilliform erythematous rash which resolved with oral corticosteroids. Four months later, she essentially had no cutaneous findings on low-dose prednisone and represented with acute onset chest pain and dyspnea. She also had an abnormal electrocardiogram suspicious for pericarditis. Her cardiac function deteriorated rapidly with near-fatal arrhythmias and ejection fractions of 10% bilaterally despite high-dose corticosteroids. She was placed on IVIG, and a left ventricular assist device was implanted within 24 hours of admission. A myocardial biopsy was performed during this surgery which showed a patchy lymphocytic infiltrate with some eosinophils. Methylprednisolone was increased to 1 g per day for 3 days and then slowly tapered. The patient was additionally placed on mycophenolate
J AM ACAD DERMATOL
AB123
P2603
Acrokeratosis neoplastica of Bazex without associated malignancy after 2 years of suggestive cutaneous findings: A case report Miranda Smith, MD, University of Oklahoma Health Science Center, Department of Dermatology, Oklahoma City, OK, United States; Renee Grau, MD, University of Oklahoma Health Science Center, Department of Dermatology, Oklahoma City, OK, United States
Treatment of toxic epidermal necrolysis with intravenous immunoglobulin: The Washington Hospital Center experience Suzanne Meyer, MD, Washington Hospital Center, Washington, DC, United States; Alan Moshell, MD, Washington Hospital Center, Washington, DC, United States; Joseph F. Sobanko, MD, Washington Hospital Center, Washington, DC, United States; Kevin Hogan, MD, Georgetown University Hospital, Washington, DC, United States; Thomas P. Nigra, MD, Washington Hospital Center, Washington, DC, United States Background: Toxic epidermal necrolysis (TEN) is a severe adverse mucocutaneous drug reaction where[30% of the total body surface area (TBSA) of skin sloughs after exposure to an inciting medication. The FaseFasL interaction is believed to play a major role in the etiology of this eruption. The use of intravenous immunoglobulin (IVIG), which has been demonstrated to block Fas-mediated keratinocyte apoptosis, has been reported in numerous case series to be of benefit in patients with TEN. However, there is also evidence to suggest the contrary and as such, the standard use of IVIG in TEN remains controversial.
Acrokeratosis neoplastica of Bazex is a rare condition which has been found to be a distinctive marker of malignancy, specifically supradiaphragmatic neoplasia. The cutaneous findings of this syndrome often precede the diagnosis of malignancy and generally the malignancy is found within months of the onset of the cutaneous manifestations. These cutaneous signs include papulosquamous lesions, hyperpigmentation, keratoderma, paronychia, and nail dystrophy. The classic finding is erythematous to violaceous patches or plaques found symmetrically on acral skin. The majority of patients will have symptomatic improvement with treatment of the underlying malignancy; however, this syndrome is otherwise resistant to treatment. We present a case of apparent Bazex syndrome with extensive work-up for malignancy over the past 2 years which has found no malignancy thus far. In addition to those of Bazex, the patient also has other classic cutaneous paraneoplastic signs including acanthosis nigricans and tripe palms, all of which arose over the preceding 2 years. Commercial support: None identified.
Objective: To perform a retrospective analysis of patients with biopsy-proven TEN treated with IVIG at our institution. Our null hypothesis was that administration of IVIG does not affect the mortality of patients with TEN. Design: A chart review was performed of all patients that carried the diagnosis of StevenseJohnson syndrome (SJS) or TEN from 1999 to 2006. Patients included in the analysis needed to meet the following criteria: [30% TBSA epidermal detachment, administration of IVIG, and histologic confirmation of the diagnosis of TEN. Administration of systemic corticosteroids was permissible in these patients; however, the concomitant use of other systemic therapies suggested to be of benefit in the setting of TEN was a criterion of exclusion. Patients who received IVIG with skin sloughing \30% TBSA (ie, SJS) were also excluded. Various parameters were recorded and analyzed and the SCORTEN was calculated for each patient included in the analysis. To determine whether the use of IVIG caused a significant reduction in mortality, a test of proportions for binomial distribution was performed, comparing expected and observed mortality overall and for each SCORTEN category. The significance level (a) was set at 0.10. Results: Twenty-one patients (12 men, 9 women) with biopsy-proven TEN were treated with cessation of the offending agent, standard wound care and IVIG at 0.4 g/kg/day for 5 consecutive days for a total dose of 2 g/kg. No severe adverse effects were observed as a consequence of IVIG infusion. Four patients died despite treatment with IVIG, resulting in a mortality rate of 19%. However, when the SCORTEN of the included patients in this study was evaluated, the expected mortality rate of our population was 37.2%. When comparing the death frequency of the sample of our 21 TEN patients to the expected death frequency, the overall cumulative probability was calculated to be statistically significant (0.0629). Conclusions: This retrospective analysis demonstrates that IVIG significantly reduced mortality in patients treated for TEN in our institution. It must be noted, however, that the results using a sample size of 21 does not have sufficient power to give conclusive results. It is recommended that a larger sample size be used in a future study to have sufficient power. Commercial support: None identified.
P2604
P2602 Sirolimus-associated lymphedema: Eight new cases Nemesha Desai, MD, St George’s Hospital, Tooting, London, United Kingdom; Peter Mortimer, MD, MBChB, St George’s Hospital, Tooting, London, United Kingdom Sirolimus (or rapamycin) is a mammalian target of rapamycin (mTOR) inhibitor with immunosuppressant and antiproliferative properties. It is licensed for use in the prophylaxis of organ rejection in adult patients who have received renal transplantation. Documented side effects include dyslipidemia, impaired wound healing, and an increase in lymphocoele formation. There are emerging reports of sirolimusassociated lymphedema involving sites local and distant to previous surgery. We report a series of eight new cases. A 57-year-old male presented with a 4-year history of right lower limb lymphedema. His symptoms began 18 months after a right iliac fossa cadaveric renal transplant and 9 months after commencing sirolimus (average dose 2 mg od). He had a history of end-stage renal failure secondary to congenital hydronephrosis and reflux, two failed renal transplants and an idiopathic hydrocoele. There was no family history of lymphedema. Imaging of the renal tract and right lower limb venous system was normal. Lymphoscintigraphy demonstrated right sided obstruction to lymph flow through the main lower limb lymphatics with rerouting through dermal collaterals. In the absence of other obvious causes, a diagnosis of sirolimus associated lymphedema was made. There was no improvement in lymphedema following drug withdrawal. We have since observed seven further cases of sirolimus associated lymphedema in transplant patients receiving sirolimus for 2 to 10 months before symptom onset. In five cases, the site of lymphedema was anatomically related to previous transplant surgery or hemodialysis access. Two cases had bilateral lymphedema. Lymphoscintigraphy universally showed obstruction to lymphatic flow through the main lymphatic channels. In contrast to the literature, none of our patients improved on drug withdrawal. The mechanism of sirolimus-associated lymphedema is unclear. Vascular endothelial growth factors (VEGF) C and D are known to play a key role in lymphatic proliferation, migration and survival. Recent studies have demonstrated that mTOR is a downstream signal in the VEGF-C pathway, suggesting that sirolimus-induced postsurgical inhibition of lymphangiogenesis and lymphatic survival may contribute to the etiology of clinical lymphedema. Commercial support: None identified.
MARCH 2009
Fulminant myocarditis as a late sequelae of DRESS syndrome Greg P. Bourgeois, University of Alabama at Birmingham, Department of Dermatology, Birmingham, AL, United States; Jennifer A. Cafardi, MD, University of Alabama at Birmingham, Department of Dermatology, Birmingham, AL, United States; Lauren C. Hughey, MD, University of Alabama at Birmingham, Department of Dermatology, Birmingham, AL, United States; Vlada Groysman, MD, University of Alabama at Birmingham, Department of Dermatology, Birmingham, AL, United States Drug rash with eosinophilia and systemic symptoms (DRESS), also known as drug hypersensitivity syndrome, is a severe cutaneous drug reaction that affects numerous organ systems and is associated with a high mortality. This eruption typically results in a rash, facial edema, lymphadenopathy, hepatitis, peripheral eosinophilia, and fever. We report two cases of fulminant myocarditis as a late sequelae of DRESS; each case of DRESS was related to sulfa-containing medications. These patients presented with myocarditis 4 to 6 months after the initial presentation of DRESS with severe chest pain and dyspnea. Both had elevated cardiac enzymes at initial evaluation, and their ventricular ejection fractions rapidly deteriorated. The first patient was a 30-year-old black female who was on both oral prednisone and intravenous immunoglobulin (IVIG) every 6 weeks at the time of presentation as treatment for her refractory, persistent symptoms of DRESS syndrome. She initially presented with a morbilliform eruption that progressed to an exfoliative erythroderma, however, her cutaneous findings were slowly improving at the time of subsequent presentation. The patient described symptoms of increasing dyspnea and acute onset chest pain. Cardiac evaluation in the emergency room revealed STelevation on the electrocardiogram and elevated cardiac enzymes. Cardiac catheterization was performed emergently and showed patent coronary vessels. Pericarditis was noted on echocardiogram, and given elevated enzymes, a myocarditis was suspected. All viral titers were negative making a viral etiology of the myocarditis less likely. The corticosteroid dose was increased during the hospitalization, however, the patient died from refractory arrhythmias. A post-mortem evaluation showed significant eosinophilic infiltration of all layers of the heart as well as complete necrosis of areas of the myocardium. The second patient was a 28-year-old black female, also with an initial morbilliform erythematous rash which resolved with oral corticosteroids. Four months later, she essentially had no cutaneous findings on low-dose prednisone and represented with acute onset chest pain and dyspnea. She also had an abnormal electrocardiogram suspicious for pericarditis. Her cardiac function deteriorated rapidly with near-fatal arrhythmias and ejection fractions of 10% bilaterally despite high-dose corticosteroids. She was placed on IVIG, and a left ventricular assist device was implanted within 24 hours of admission. A myocardial biopsy was performed during this surgery which showed a patchy lymphocytic infiltrate with some eosinophils. Methylprednisolone was increased to 1 g per day for 3 days and then slowly tapered. The patient was additionally placed on mycophenolate
J AM ACAD DERMATOL
AB123