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Cutaneous side effects of EGFR inhibitors: A study of 10 patients
P1112
P1114
Cutaneous side effects of EGFR inhibitors: A study of 10 patients Felicidade Santiago, MD, Dermatology Department, Coimbra, Portugal; Ame´rico Figueiredo, MD, PhD, Dermatology Department, Coimbra, Portugal; Margarida Gonc¸alo, MD, Dermatology Department, Coimbra, Portugal Introduction: Epidermal growth factor receptor (EGFR) inhibitors, both the monoclonal antibody—cetuximab—and the tyrosine kinase inhibitor—erlotinib—approved for patients with colorectal and lung cancer refractory or intolerant to chemotherapy are associated with peculiar cutaneous side effects. A priori identification of patients who are more prone to develop skin toxicity is not yet available.
Erythema nodosum due to azothiaprine in a 13-year-old male with Crohn disease Risa Behar Ross, DO, Largo Medical Center, Largo, FL, United States; Richard Miller, DO, Largo Medical Center, Largo, FL, United States
Objectives: Our aim was to describe the cutaneous side effects of EGFR inhibitors and their management. Methods: Between March 2006 and March 2009, our dermatology department studied 10 patients (7 males and 3 females) with a mean age of 61.9 years (range, 5077), under therapy with cetuximab and erlotinib (5 cases each). The type of adverse reaction, interval between introduction of EGFR inhibitor and skin symptoms, treatment, and evolution were assessed. Results: The most common side effect, observed in nine patients, was a papulopustular eruption, involving mainly the face, upper chest, and back. It appeared within 1 to 6 weeks (mean, 15.6 days) after onset of EGFR inhibitor. All patients were treated with oral antibiotic (minocycline or doxycycline) associated with a topical treatment (metronidazole, benzoyl peroxide, or corticosteroids), with improvement of the lesions in all patients and a very good response in six patients. One patient presented paronychia with periungueal pyogenic granulomaelike lesions associated with erlotinib, which improved slightly on topical antibiotics and corticosteroids. Another patient had also asteatotic eczema, mainly in the trunk, 8 weeks after initiation of erlotinib, with a good response to emollients. In the majority of patients, the EGFR inhibitor was maintained in the same dose, except in two who reduced erlotinib to 100 mg/day and in two other who suspended use of the drug because of neoplastic disease progression.
Erythema nodosum is a well known form of panniculitis. It typically presents as erythematous, subcutaneous, firm, tender, warm nodules on the lower extremities. Many causes of erythema nodosum have been described, including infectious etiologies, medications, and inflammatory bowel disease. Erythema nodosum often gives clinical clues to systemic disease. The onset of erythema nodosum frequently correlates with a flare of inflammatory bowel disease, a well reported association. Certain medications, including oral contraceptives, sulfonamides, penicillin, bromides, and iodides, have all been repeatedly linked to erythema nodosum. We present the case of a 13-year-old male with Crohn disease who developed an eruption clinically consistent with erythema nodosum after initiating treatment with azothiaprine for his inflammatory bowel disease. The development of his erythema nodosum was not associated with a flare of his inflammatory bowel disease and his gastrointestinal symptoms were well controlled at time of presentation. The eruption did resolve after discontinuation of the azothiaprine and did reappear with rechallenge of the medication 4 weeks later. There are very few reported cases of azothiaprine-induced erythema nodosum. Practioners prescribing this medication should be aware of this potential side effect and recognize that erythema nodosum may not be solely caused by underlying inflammatory bowel disease. Commercial support: None identified.
Discussion: Although the number of patients treated is small, in our experience the papulopustular eruption responded well to topical treatment and oral tetracycline, whereas emollients improved skin xerosis. The expanding use of this new targeted therapy requires that dermatologists became familiar with the associated cutaneous reactions and promote an interdisciplinary approach with the oncology department to ensure timely intervention and follow-up. Commercial support: None identified.
P1115
P1113 Multisystem Langerhans cell histiocytosis in an adult presenting with vulvar lesions Tiffany Brazeal, MD, Mayo Clinic, Scottsdale, AZ, United States; David DiCaudo, MD, Mayo Clinic, Scottsdale, AZ, United States; Megan Weber, MD, Mayo Clinic, Scottsdale, AZ, United States; Karen Warschaw, MD, Mayo Clinic, Scottsdale, AZ, United States A 65-year-old white female with a history of diabetes mellitus, obesity, and prior tobacco abuse presented with a 1-year history of dysuria, frequent urinary tract infections, and pruritic vulvar lesions. The vulvar rash had previously been treated as a suspected yeast infection with several courses of antibiotics and antifungals. Over time, the rash progressed to involve the inframammary folds, groin, axillae, and scalp. Biopsy of the vulvar lesions revealed Langerhans cell histiocytosis (LCH) and the patient was referred to our dermatology clinic. The skin examination revealed numerous 3- to 5-mm indurated monomorphic red papules in the inframmamary folds and groin. The postauricular scalp showed crusted pink papules extending along the hairline. Biopsies from the vulva and inframmary fold revealed a dense infiltrate of mononuclear cells with cleaved nuclei and scattered eosinophils. The infiltrate strongly expressed S-100 and CD1a and were negative for CD68, confirming the diagnosis of LCH. CT scan revealed numerous bilateral pulmonary nodules. Pulmonary wedge biopsies were consistent with pulmonary LCH. Skeletal survey and bone marrow biopsy were negative for evidence of involvement. The occurrence of LCH in adults is exceedingly rare and the incidence may approach one to two cases per million. The disease may affect the skin and other organs. Lung involvement in children is rare, but is often the main manifestation of LCH in adults, especially in those with a history of tobacco abuse. Although LCH in adults is rare, it should be considered in the differential diagnosis when treating chronic and refractory intertriginous lesions. In such cases, it is necessary to perform a biopsy, rule out systemic involvement, and survey the patient over time. Commercial support: None identified.
MARCH 2010
Dermatology life quality index (DLQI) in HIV-associated lipodistrophy patients Patricia Contreras-Ferrer, MD, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain; Cristina Rodriguez-Garcia, MD, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain; Marta Garcia-Bustinduy, MD, PhD, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain; Nuria Perez-Robayna, MD, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain; Sorahaya GonzalezHernandez, MD, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain Introduction: HIV-associated lipodystrophy is a skin condition that is characterized by the loss of subcutaneous fat. Although the exact mechanism of this is unknown, it is believed that lipodystrophy in HIV patients is caused by antiretroviral medications. Patients often present with fat loss in the face, buttocks, arms, and legs. There is also fat accumulation in various body parts, like fat deposits in their upper backs. The breast sizes of patients (both male and female) tend to increase. In addition, patients develop abdominal obesity. In this context, therapy-related body changes gain in importance, in light of the psychological distress they cause and of their association with adherence to treatment. Methods: We have performed a cross-sectional observational study in 30 patients affected with HIV-associated lipodystrophy. The presence of lipodystrophy was defined by clinical criteria. The patients were evaluated with the Dermatology Life Quality Index questionnaire (DLQI) using a like control group of 10 HIV patients without lipodystrophy. In addition, dates of age and sex were registered. Results: Eighty percent were male in both groups. The mean age of patients with lipodystrophy was 44.7 years (male:female ratio, 44.5:44.8). Patients with lipodystrophy presented a low puntuation in DLQI (the mean punctuation was 2.7). On the other hand, the control group (patients without lipodystrophy) obtained 2.3 points in DLQI with a mean age of 34.7 years (male:female ratio, 29.5:36). These differences were not statistically significant (P ¼ .4). Conclusion: We have observed a small effect on patients’ life in both groups (with and without lypodystrophy). These data suggest that the impact of quality of life in HIV-associated lipodystrophy depends on certain patients’ characteristics, rather than on the presence of lipodystrophy itself. Nonetheless, our study is limited by the small sample size. Commercial support: None identified.
J AM ACAD DERMATOL
AB29
P1114
Cutaneous side effects of EGFR inhibitors: A study of 10 patients Felicidade Santiago, MD, Dermatology Department, Coimbra, Portugal; Ame´rico Figueiredo, MD, PhD, Dermatology Department, Coimbra, Portugal; Margarida Gonc¸alo, MD, Dermatology Department, Coimbra, Portugal Introduction: Epidermal growth factor receptor (EGFR) inhibitors, both the monoclonal antibody—cetuximab—and the tyrosine kinase inhibitor—erlotinib—approved for patients with colorectal and lung cancer refractory or intolerant to chemotherapy are associated with peculiar cutaneous side effects. A priori identification of patients who are more prone to develop skin toxicity is not yet available.
Erythema nodosum due to azothiaprine in a 13-year-old male with Crohn disease Risa Behar Ross, DO, Largo Medical Center, Largo, FL, United States; Richard Miller, DO, Largo Medical Center, Largo, FL, United States
Objectives: Our aim was to describe the cutaneous side effects of EGFR inhibitors and their management. Methods: Between March 2006 and March 2009, our dermatology department studied 10 patients (7 males and 3 females) with a mean age of 61.9 years (range, 5077), under therapy with cetuximab and erlotinib (5 cases each). The type of adverse reaction, interval between introduction of EGFR inhibitor and skin symptoms, treatment, and evolution were assessed. Results: The most common side effect, observed in nine patients, was a papulopustular eruption, involving mainly the face, upper chest, and back. It appeared within 1 to 6 weeks (mean, 15.6 days) after onset of EGFR inhibitor. All patients were treated with oral antibiotic (minocycline or doxycycline) associated with a topical treatment (metronidazole, benzoyl peroxide, or corticosteroids), with improvement of the lesions in all patients and a very good response in six patients. One patient presented paronychia with periungueal pyogenic granulomaelike lesions associated with erlotinib, which improved slightly on topical antibiotics and corticosteroids. Another patient had also asteatotic eczema, mainly in the trunk, 8 weeks after initiation of erlotinib, with a good response to emollients. In the majority of patients, the EGFR inhibitor was maintained in the same dose, except in two who reduced erlotinib to 100 mg/day and in two other who suspended use of the drug because of neoplastic disease progression.
Erythema nodosum is a well known form of panniculitis. It typically presents as erythematous, subcutaneous, firm, tender, warm nodules on the lower extremities. Many causes of erythema nodosum have been described, including infectious etiologies, medications, and inflammatory bowel disease. Erythema nodosum often gives clinical clues to systemic disease. The onset of erythema nodosum frequently correlates with a flare of inflammatory bowel disease, a well reported association. Certain medications, including oral contraceptives, sulfonamides, penicillin, bromides, and iodides, have all been repeatedly linked to erythema nodosum. We present the case of a 13-year-old male with Crohn disease who developed an eruption clinically consistent with erythema nodosum after initiating treatment with azothiaprine for his inflammatory bowel disease. The development of his erythema nodosum was not associated with a flare of his inflammatory bowel disease and his gastrointestinal symptoms were well controlled at time of presentation. The eruption did resolve after discontinuation of the azothiaprine and did reappear with rechallenge of the medication 4 weeks later. There are very few reported cases of azothiaprine-induced erythema nodosum. Practioners prescribing this medication should be aware of this potential side effect and recognize that erythema nodosum may not be solely caused by underlying inflammatory bowel disease. Commercial support: None identified.
Discussion: Although the number of patients treated is small, in our experience the papulopustular eruption responded well to topical treatment and oral tetracycline, whereas emollients improved skin xerosis. The expanding use of this new targeted therapy requires that dermatologists became familiar with the associated cutaneous reactions and promote an interdisciplinary approach with the oncology department to ensure timely intervention and follow-up. Commercial support: None identified.
P1115
P1113 Multisystem Langerhans cell histiocytosis in an adult presenting with vulvar lesions Tiffany Brazeal, MD, Mayo Clinic, Scottsdale, AZ, United States; David DiCaudo, MD, Mayo Clinic, Scottsdale, AZ, United States; Megan Weber, MD, Mayo Clinic, Scottsdale, AZ, United States; Karen Warschaw, MD, Mayo Clinic, Scottsdale, AZ, United States A 65-year-old white female with a history of diabetes mellitus, obesity, and prior tobacco abuse presented with a 1-year history of dysuria, frequent urinary tract infections, and pruritic vulvar lesions. The vulvar rash had previously been treated as a suspected yeast infection with several courses of antibiotics and antifungals. Over time, the rash progressed to involve the inframammary folds, groin, axillae, and scalp. Biopsy of the vulvar lesions revealed Langerhans cell histiocytosis (LCH) and the patient was referred to our dermatology clinic. The skin examination revealed numerous 3- to 5-mm indurated monomorphic red papules in the inframmamary folds and groin. The postauricular scalp showed crusted pink papules extending along the hairline. Biopsies from the vulva and inframmary fold revealed a dense infiltrate of mononuclear cells with cleaved nuclei and scattered eosinophils. The infiltrate strongly expressed S-100 and CD1a and were negative for CD68, confirming the diagnosis of LCH. CT scan revealed numerous bilateral pulmonary nodules. Pulmonary wedge biopsies were consistent with pulmonary LCH. Skeletal survey and bone marrow biopsy were negative for evidence of involvement. The occurrence of LCH in adults is exceedingly rare and the incidence may approach one to two cases per million. The disease may affect the skin and other organs. Lung involvement in children is rare, but is often the main manifestation of LCH in adults, especially in those with a history of tobacco abuse. Although LCH in adults is rare, it should be considered in the differential diagnosis when treating chronic and refractory intertriginous lesions. In such cases, it is necessary to perform a biopsy, rule out systemic involvement, and survey the patient over time. Commercial support: None identified.
MARCH 2010
Dermatology life quality index (DLQI) in HIV-associated lipodistrophy patients Patricia Contreras-Ferrer, MD, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain; Cristina Rodriguez-Garcia, MD, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain; Marta Garcia-Bustinduy, MD, PhD, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain; Nuria Perez-Robayna, MD, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain; Sorahaya GonzalezHernandez, MD, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain Introduction: HIV-associated lipodystrophy is a skin condition that is characterized by the loss of subcutaneous fat. Although the exact mechanism of this is unknown, it is believed that lipodystrophy in HIV patients is caused by antiretroviral medications. Patients often present with fat loss in the face, buttocks, arms, and legs. There is also fat accumulation in various body parts, like fat deposits in their upper backs. The breast sizes of patients (both male and female) tend to increase. In addition, patients develop abdominal obesity. In this context, therapy-related body changes gain in importance, in light of the psychological distress they cause and of their association with adherence to treatment. Methods: We have performed a cross-sectional observational study in 30 patients affected with HIV-associated lipodystrophy. The presence of lipodystrophy was defined by clinical criteria. The patients were evaluated with the Dermatology Life Quality Index questionnaire (DLQI) using a like control group of 10 HIV patients without lipodystrophy. In addition, dates of age and sex were registered. Results: Eighty percent were male in both groups. The mean age of patients with lipodystrophy was 44.7 years (male:female ratio, 44.5:44.8). Patients with lipodystrophy presented a low puntuation in DLQI (the mean punctuation was 2.7). On the other hand, the control group (patients without lipodystrophy) obtained 2.3 points in DLQI with a mean age of 34.7 years (male:female ratio, 29.5:36). These differences were not statistically significant (P ¼ .4). Conclusion: We have observed a small effect on patients’ life in both groups (with and without lypodystrophy). These data suggest that the impact of quality of life in HIV-associated lipodystrophy depends on certain patients’ characteristics, rather than on the presence of lipodystrophy itself. Nonetheless, our study is limited by the small sample size. Commercial support: None identified.
J AM ACAD DERMATOL
AB29