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Imatinib-induced psoriasiform drug eruption: 2 cases
P1156
P1158
Erythropoietic protoporphyria: An unusual skin presentation Khadija Khadir, Ibn Rochd UHC, Casablanca, Anfa, Morocco; Hakima Benchikhi, Ibn Rochd UHC, Casablanca, Anfa, Morocco; Soumia el Mabady, Ibn Rochd UHC, Casablanca, Anfa, Morocco Introduction: Erythropoietic protoporphyria (EPP) is a rare genodermatosis that is caused by decreased activity of the enzyme ferrochelatasis, the terminal enzyme of the heme biosynthetic pathway. We report case of EPP where melanoderma was the only evoking sign. Observation: A 9-month-old girl of consanguines parents consulted in March 2008. Her brother had similar disease at the age of 2 years and died at 3 years because of deshydratation complicating chronic diarrhea. History begun at the age of 3 months. Isolate melanoderma of the face and the upper and lower limb extension faces appeared with no itching, nor transit disorders with no previous vesiculobullous lesions, nor abdomen pains, nor neuropsychiatric syndrome. At examination, melanoderma of sun-exposed areas were combined to a discrete edema of the hand backs. No skin frailty was noticed, nor face dysmorphy signs, nor dental or pilary anomalies. The diagnosis of suprarenal failure was evoked but rapidly discarded due to the exclusive spread to sun exposed area of the melanoderma and the negative hormone dosages (ACTHemorning cortisol). Allgrove syndrome was also evoked but no alachrima was found nor any achalasia. The search for malabsorption syndrome and avitaminosis leading to pellagra was negative (vitamin PP normal). Porphyrin dosages showed the increase of the blood protoporphyrin rate (130 g/L, normal,\0.01 g/L; or 1.14 g/gHb, normal,\0.80 g/gHb). Blood coproporphyrin was normal as well as the urine dosages of the porphobilinogen of the uroporphyrin and of the coproporphyrin. The patient presents microcytic normochromia anemia with normal rates of transaminases. Thus, EPP diagnosis was retained. As therapy, the patient underwent external photoprotection.
An analysis of efficacy data from five phase III studies of BoNT-A for the treatment of glabellar lines Leslie Baumann, MD, Cosmetic Medicine and Research Institute, Miami Beach, FL, United States; Fredric Brandt, MD, Dermatology Research Institute, LLC, Coral Gables, FL, United States; Michael Kane, MD, Kane Plastic Surgery, New York, NY, United States
Discussion: The difficulty of the diagnosis in our patient is because of the isolated melanoderma. Patients usually experience itching and burning, and develop erythema even after brief exposure to bright light. EPP differs from other skin porphyrias mainly by absence of increase of urinary porphyrin. This was the case of our patient. The evolution is usually favorable with regression of thrusts at adulthood. However, the hepatobiliary affection present in about 25% of the cases, restrains the prognosis. The death of the brother could be retated to a non explored hepatic affection. There is no therapeutic consensus. The only preventive measure to take is sun eviction. The genic therapy can be a promise for definite treatment. Commercial support: None identified.
Background: A new US botulinum neurotoxin type A formulation (BoNT-A; Dysport [abobotulinumtoxinA]; Medicis Aesthetics, Scottsdale, AZ) has recently been approved by the US Food and Drug Administration for the treatment of moderate to severe glabellar lines. Objective: We describe the results of five phase III studies of BoNT-A for the treatment of glabellar lines. Methods: Three double-blind, multicenter, randomized, placebo-controlled studies enrolled ethnically diverse healthy adults with glabellar lines of at least moderate severity at maximum frown. In these studies, patients were followed for up to 180 days after treatment. The fixed-dose, single-treatment study randomized 158 patients to receive placebo or one dose of BoNT-A 50 U. The fixed-dose, repeattreatment study randomized 311 patients to assess treatment following the prior BoNT-A treatment of 50 U. The variable-dose study randomized 816 patients to receive placebo or a single variable dose (50-80 U, based on gender and assessment of muscle mass). Clinical evaluations were performed on days 14 and 30 and monthly thereafter. The primary endpoint was a response defined as a composite 21 grade improvement, at day 30 from baseline, on the wrinkle severity rating scale (WSRS): from 2 to 0, or from 3 to 0 or 1 (where 3 ¼ severe wrinkles/severe, 2 ¼ moderate wrinkles/moderate, 1 ¼ mild wrinkles/mild, and 0 ¼ no wrinkles/none), for both the blinded evaluator’s/blinded investigator’s and patient’s assessments. Results: Patients (1116 total; 720 BoNT-A, 396 placebo) given BoNT-A received 50 to 80 U of treatment. The median duration of response was 85 days for fixed dosing and 109 days for variable dosing. Similar efficacy occurred at doses adjusted for gender and muscle mass, although males required higher doses than females in the variabledose study. Responses appeared as early as 24 hours, with a median time to onset of 3 days. Extension studies evaluated 1200 patients for 13 months and 768 patients in an interim analysis for 24 months. Maintenance of efficacy was seen after multiple cycles, indicating a lack of tolerance. Conclusions: BoNT-A significantly improved moderate to severe glabellar lines compared with placebo, with onset seen as soon as 24 hours after treatment and a median duration of effect of 85 or 109 days for fixed or variable dosing, respectively. Commercial support: None identified.
P1157 Imatinib-induced psoriasiform drug eruption: 2 cases Samira Belyamani, Dermatology Department, Ibn Rochd UHC, Casablanca, Anfa, Morocco; Hakima Benchikhi, Dermatology Department, Ibn Rochd UHC, Casablanca, Anfa, Morocco; Samira Skali, Dermatology Department, Ibn Rochd UHC, Casablanca, Anfa, Morocco; Sofia Azouzi, Pathology Department, Ibn Rochd UHC, Casablanca, Anfa, Morocco Introduction: Imatinib (Glivec*) is an inhibitor of tyrosine kinase, mainly used in the treatment of chronic myeloid leukemia and some malignant stromal gastrointestinal tumors. Currently, this molecule has several indications, and its cutaneous side effects are becoming better known. We report two cases of psoriasiform drug-induced dermatitis. Case reports: A 38-year-old woman presented in October 2008 for a malignant stromal intestinal tumor; she was given imatinib (Glivec*) at a dose of 400 mg/day. Three months later, she developed widespread psoriasiform itching erythematous squamous lesions. Skin histology showed lichenoid vasculitis. All lesions disappeared after symptomatic treatment and Glivec* was maintained. Our second case was a 37-year-old man who was treated for chronic myeloid leukemia with Glivec* at the dose of 400 mg/day. Three months later, he presented with facial edema, cheilitis, and generalized itching erythematous squamous lesions. The skin histology showed an aspect of lichenoid drug-induced dermatitis. Imatinib was stopped for 6 months, with complete disappearance of skin lesions under symptomatic treatment. The reintroduction of Glivec* was required, and the evolution was marked by the recurrence of psoriasiform eruption after 3 months. The therapeutic decision was to maintain Glivec* associated with symptomatic treatment (topical corticosteroids). The evolution was marked by a complete skin bleaching. Discussion: Imatinib has been imputed in our two patients; however, considering the risk/benefit ratio, this drug has not been arrested in both cases. The cutaneous side effects of this molecule are relatively common, occurring in 11% to 67% of cases, and include mild to moderate itch, maculopapular exanthema, and facial edema. However, more severe drug-induced dermatoses have been reported, including DRESS syndrome, StevenseJohnson syndrome, acute generalized exanthematous pustulosis, and purpuric vasculitis. Recently, particular varieties were also published, including bleeding under the nail, pigmentary disorders, drug lymphoma, porphyria cutanea tarda, profuse cutaneous lichen, and oral erosive lichen. Our cases are the first two observations of psoriasiform drug-induced dermatitis which we classify as being of moderate severity. The time to onset of skin reactions is variable, ranging from 20 days to 1 year. In our cases, this period was 3 months. The reccurence after reintroduction in the second patient was also 3 months. For many authors, these reactions result from a dose-dependent effect of imatinib, they are more frequent and more severe with higher doses (600-800 mg/d), and this suggests a pharmacologic effect rather than an immunologic one. However, for our patients treated with doses of 400 mg/day, there is the question of an immunologic effect. The resolution of drug-induced dermatitis despite the maintenance of Glivec* is another argument of immunologic effect. Conclusion: Imatinib should be considered as a drug that induced severe cutaneous reactions. Currently, its use in nonhematologic indications may increase the number of serious drug-induced dermatitis. Commercial support: None identified.
AB40
J AM ACAD DERMATOL
P1159 Generalized perforating granuloma annulare Nektarios Lountzis, MD, Geisinger Medical Center, Danville, PA, United States; Dirk Elston, MD, Geisinger Medical Center, Danville, PA, United States; Tammie Ferringer, MD, Geisinger Medical Center, Danville, PA, United States Granuloma annulare (GA) is a benign dermatosis classically characterized by papules assuming an annular configuration and histologically defined by degenerated collagen surrounded by palisading histiocytes. It can be divided into several subtypes, including a generalized perforating GA (GPGA) variant. Herein, we present a case of an otherwise healthy 15-year-old white male with a several 3- to 7mm pink waxy umbilicated papules with central crusting that progressed over his lower extremities in six months. Family history was significant for diabetes mellitus in a maternal aunt. Histopathology revealed an interstitial infiltrate of histiocytes and giant cells interlaced between collagen bundles and overlying a central epithelial lined channel. In areas, there was a well developed palisade of histiocytes surrounding a faint central mucinous deposition highlighted by colloidal iron. A diagnosis of GPGA was rendered and 1 month of pentoxifylline 400 mg PO TID resulted in no clinical change. The papules slowly progressed to the upper extremities, and his medication was changed to clobetasol topically but the patient was subsequently lost to follow-up. GPGA was first described in 1973 and since then approximately 20 cases have been reported, including familial forms. In children, it generally does not have an association with diabetes but the association is stronger in the elderly, as seen in non-perforating generalized GA. Overall, GPGA represents an interesting and rare variant of a common dermatosis. Commercial support: None identified.
MARCH 2010
P1158
Erythropoietic protoporphyria: An unusual skin presentation Khadija Khadir, Ibn Rochd UHC, Casablanca, Anfa, Morocco; Hakima Benchikhi, Ibn Rochd UHC, Casablanca, Anfa, Morocco; Soumia el Mabady, Ibn Rochd UHC, Casablanca, Anfa, Morocco Introduction: Erythropoietic protoporphyria (EPP) is a rare genodermatosis that is caused by decreased activity of the enzyme ferrochelatasis, the terminal enzyme of the heme biosynthetic pathway. We report case of EPP where melanoderma was the only evoking sign. Observation: A 9-month-old girl of consanguines parents consulted in March 2008. Her brother had similar disease at the age of 2 years and died at 3 years because of deshydratation complicating chronic diarrhea. History begun at the age of 3 months. Isolate melanoderma of the face and the upper and lower limb extension faces appeared with no itching, nor transit disorders with no previous vesiculobullous lesions, nor abdomen pains, nor neuropsychiatric syndrome. At examination, melanoderma of sun-exposed areas were combined to a discrete edema of the hand backs. No skin frailty was noticed, nor face dysmorphy signs, nor dental or pilary anomalies. The diagnosis of suprarenal failure was evoked but rapidly discarded due to the exclusive spread to sun exposed area of the melanoderma and the negative hormone dosages (ACTHemorning cortisol). Allgrove syndrome was also evoked but no alachrima was found nor any achalasia. The search for malabsorption syndrome and avitaminosis leading to pellagra was negative (vitamin PP normal). Porphyrin dosages showed the increase of the blood protoporphyrin rate (130 g/L, normal,\0.01 g/L; or 1.14 g/gHb, normal,\0.80 g/gHb). Blood coproporphyrin was normal as well as the urine dosages of the porphobilinogen of the uroporphyrin and of the coproporphyrin. The patient presents microcytic normochromia anemia with normal rates of transaminases. Thus, EPP diagnosis was retained. As therapy, the patient underwent external photoprotection.
An analysis of efficacy data from five phase III studies of BoNT-A for the treatment of glabellar lines Leslie Baumann, MD, Cosmetic Medicine and Research Institute, Miami Beach, FL, United States; Fredric Brandt, MD, Dermatology Research Institute, LLC, Coral Gables, FL, United States; Michael Kane, MD, Kane Plastic Surgery, New York, NY, United States
Discussion: The difficulty of the diagnosis in our patient is because of the isolated melanoderma. Patients usually experience itching and burning, and develop erythema even after brief exposure to bright light. EPP differs from other skin porphyrias mainly by absence of increase of urinary porphyrin. This was the case of our patient. The evolution is usually favorable with regression of thrusts at adulthood. However, the hepatobiliary affection present in about 25% of the cases, restrains the prognosis. The death of the brother could be retated to a non explored hepatic affection. There is no therapeutic consensus. The only preventive measure to take is sun eviction. The genic therapy can be a promise for definite treatment. Commercial support: None identified.
Background: A new US botulinum neurotoxin type A formulation (BoNT-A; Dysport [abobotulinumtoxinA]; Medicis Aesthetics, Scottsdale, AZ) has recently been approved by the US Food and Drug Administration for the treatment of moderate to severe glabellar lines. Objective: We describe the results of five phase III studies of BoNT-A for the treatment of glabellar lines. Methods: Three double-blind, multicenter, randomized, placebo-controlled studies enrolled ethnically diverse healthy adults with glabellar lines of at least moderate severity at maximum frown. In these studies, patients were followed for up to 180 days after treatment. The fixed-dose, single-treatment study randomized 158 patients to receive placebo or one dose of BoNT-A 50 U. The fixed-dose, repeattreatment study randomized 311 patients to assess treatment following the prior BoNT-A treatment of 50 U. The variable-dose study randomized 816 patients to receive placebo or a single variable dose (50-80 U, based on gender and assessment of muscle mass). Clinical evaluations were performed on days 14 and 30 and monthly thereafter. The primary endpoint was a response defined as a composite 21 grade improvement, at day 30 from baseline, on the wrinkle severity rating scale (WSRS): from 2 to 0, or from 3 to 0 or 1 (where 3 ¼ severe wrinkles/severe, 2 ¼ moderate wrinkles/moderate, 1 ¼ mild wrinkles/mild, and 0 ¼ no wrinkles/none), for both the blinded evaluator’s/blinded investigator’s and patient’s assessments. Results: Patients (1116 total; 720 BoNT-A, 396 placebo) given BoNT-A received 50 to 80 U of treatment. The median duration of response was 85 days for fixed dosing and 109 days for variable dosing. Similar efficacy occurred at doses adjusted for gender and muscle mass, although males required higher doses than females in the variabledose study. Responses appeared as early as 24 hours, with a median time to onset of 3 days. Extension studies evaluated 1200 patients for 13 months and 768 patients in an interim analysis for 24 months. Maintenance of efficacy was seen after multiple cycles, indicating a lack of tolerance. Conclusions: BoNT-A significantly improved moderate to severe glabellar lines compared with placebo, with onset seen as soon as 24 hours after treatment and a median duration of effect of 85 or 109 days for fixed or variable dosing, respectively. Commercial support: None identified.
P1157 Imatinib-induced psoriasiform drug eruption: 2 cases Samira Belyamani, Dermatology Department, Ibn Rochd UHC, Casablanca, Anfa, Morocco; Hakima Benchikhi, Dermatology Department, Ibn Rochd UHC, Casablanca, Anfa, Morocco; Samira Skali, Dermatology Department, Ibn Rochd UHC, Casablanca, Anfa, Morocco; Sofia Azouzi, Pathology Department, Ibn Rochd UHC, Casablanca, Anfa, Morocco Introduction: Imatinib (Glivec*) is an inhibitor of tyrosine kinase, mainly used in the treatment of chronic myeloid leukemia and some malignant stromal gastrointestinal tumors. Currently, this molecule has several indications, and its cutaneous side effects are becoming better known. We report two cases of psoriasiform drug-induced dermatitis. Case reports: A 38-year-old woman presented in October 2008 for a malignant stromal intestinal tumor; she was given imatinib (Glivec*) at a dose of 400 mg/day. Three months later, she developed widespread psoriasiform itching erythematous squamous lesions. Skin histology showed lichenoid vasculitis. All lesions disappeared after symptomatic treatment and Glivec* was maintained. Our second case was a 37-year-old man who was treated for chronic myeloid leukemia with Glivec* at the dose of 400 mg/day. Three months later, he presented with facial edema, cheilitis, and generalized itching erythematous squamous lesions. The skin histology showed an aspect of lichenoid drug-induced dermatitis. Imatinib was stopped for 6 months, with complete disappearance of skin lesions under symptomatic treatment. The reintroduction of Glivec* was required, and the evolution was marked by the recurrence of psoriasiform eruption after 3 months. The therapeutic decision was to maintain Glivec* associated with symptomatic treatment (topical corticosteroids). The evolution was marked by a complete skin bleaching. Discussion: Imatinib has been imputed in our two patients; however, considering the risk/benefit ratio, this drug has not been arrested in both cases. The cutaneous side effects of this molecule are relatively common, occurring in 11% to 67% of cases, and include mild to moderate itch, maculopapular exanthema, and facial edema. However, more severe drug-induced dermatoses have been reported, including DRESS syndrome, StevenseJohnson syndrome, acute generalized exanthematous pustulosis, and purpuric vasculitis. Recently, particular varieties were also published, including bleeding under the nail, pigmentary disorders, drug lymphoma, porphyria cutanea tarda, profuse cutaneous lichen, and oral erosive lichen. Our cases are the first two observations of psoriasiform drug-induced dermatitis which we classify as being of moderate severity. The time to onset of skin reactions is variable, ranging from 20 days to 1 year. In our cases, this period was 3 months. The reccurence after reintroduction in the second patient was also 3 months. For many authors, these reactions result from a dose-dependent effect of imatinib, they are more frequent and more severe with higher doses (600-800 mg/d), and this suggests a pharmacologic effect rather than an immunologic one. However, for our patients treated with doses of 400 mg/day, there is the question of an immunologic effect. The resolution of drug-induced dermatitis despite the maintenance of Glivec* is another argument of immunologic effect. Conclusion: Imatinib should be considered as a drug that induced severe cutaneous reactions. Currently, its use in nonhematologic indications may increase the number of serious drug-induced dermatitis. Commercial support: None identified.
AB40
J AM ACAD DERMATOL
P1159 Generalized perforating granuloma annulare Nektarios Lountzis, MD, Geisinger Medical Center, Danville, PA, United States; Dirk Elston, MD, Geisinger Medical Center, Danville, PA, United States; Tammie Ferringer, MD, Geisinger Medical Center, Danville, PA, United States Granuloma annulare (GA) is a benign dermatosis classically characterized by papules assuming an annular configuration and histologically defined by degenerated collagen surrounded by palisading histiocytes. It can be divided into several subtypes, including a generalized perforating GA (GPGA) variant. Herein, we present a case of an otherwise healthy 15-year-old white male with a several 3- to 7mm pink waxy umbilicated papules with central crusting that progressed over his lower extremities in six months. Family history was significant for diabetes mellitus in a maternal aunt. Histopathology revealed an interstitial infiltrate of histiocytes and giant cells interlaced between collagen bundles and overlying a central epithelial lined channel. In areas, there was a well developed palisade of histiocytes surrounding a faint central mucinous deposition highlighted by colloidal iron. A diagnosis of GPGA was rendered and 1 month of pentoxifylline 400 mg PO TID resulted in no clinical change. The papules slowly progressed to the upper extremities, and his medication was changed to clobetasol topically but the patient was subsequently lost to follow-up. GPGA was first described in 1973 and since then approximately 20 cases have been reported, including familial forms. In children, it generally does not have an association with diabetes but the association is stronger in the elderly, as seen in non-perforating generalized GA. Overall, GPGA represents an interesting and rare variant of a common dermatosis. Commercial support: None identified.
MARCH 2010