ABSTRACT
Vemurafenib is a newly licensed target-directed medication. It has been proven to improve the survival of patients with metastatic melanoma and the BRAF(V600E) mutation; however, adverse cutaneous reactions are frequent. Few cases of life-threatening severe cutaneous adverse reactions (SCARs) induced by vemurafenib have been reported. Dabrafenib, another selective BRAF inhibitor, has been licensed recently as an alternative drug with the same indications. From a molecular point of view, both vemurafenib and dabrafenib contain a sulfonamide group; cross-reactivity to sulfonamide compounds has been reported in allergic patients. We report on a patient with vemurafenib-induced toxic epidermal necrolysis (TEN). In vitro analysis of lymphocyte reactivity to vemurafenib showed positive results, confirming drug causality. In addition, lymphocytes from the patient reacted to dabrafenib and to the antibiotic sulfonamide drug sulfamethoxazole. Moreover, lymphocytes from two patients with cutaneous adverse reactions to sulfamethoxazole also reacted to vemurafenib and dabrafenib in vitro. These data strongly suggest that there might be clinical cross-reactivity between BRAF inhibitors and sulfonamides in some patients. Thus, precautions should be taken to avoid sulfonamide drugs as much as possible in patients showing serious hypersensitivity reactions to vemurafenib and vice versa.
Subject(s)
Antineoplastic Agents/adverse effects , Indoles/adverse effects , Stevens-Johnson Syndrome/etiology , Sulfonamides/adverse effects , Aged , Drug Interactions , Drug Therapy, Combination , Humans , Imidazoles/adverse effects , Male , Melanoma/drug therapy , Oximes/adverse effects , Protein Kinase Inhibitors/adverse effects , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Pyridones/adverse effects , Pyrimidinones/adverse effects , Skin Neoplasms/drug therapy , VemurafenibABSTRACT
No disponible
Subject(s)
Humans , Male , Adult , Vitiligo/chemically induced , Vitiligo/complications , Vitiligo/immunology , Immunotherapy/adverse effects , Immunotherapy/methods , Pollen/adverse effects , Poaceae/adverse effects , Allergens/immunology , Skin Tests/methods , Drug Hypersensitivity/complications , Drug Hypersensitivity/drug therapyABSTRACT
No disponible
Subject(s)
Male , Humans , Melanoma/complications , Dermatitis/complications , Skin Diseases/chemically induced , Dermatologic Agents/adverse effects , Dermatologic Agents/toxicity , Melanoma/diagnosis , Melanoma/therapySubject(s)
Antineoplastic Agents/adverse effects , Indoles/adverse effects , Protein Kinase Inhibitors/adverse effects , Stevens-Johnson Syndrome/etiology , Sulfonamides/adverse effects , Aged , Antibodies, Monoclonal/therapeutic use , Antineoplastic Agents/therapeutic use , Combined Modality Therapy , Cyclosporine/therapeutic use , Drug Substitution , Humans , Indoles/therapeutic use , Ipilimumab , Lung Neoplasms/drug therapy , Lung Neoplasms/embryology , Lung Neoplasms/radiotherapy , Lung Neoplasms/secondary , Male , Melanoma/drug therapy , Melanoma/enzymology , Melanoma/radiotherapy , Melanoma/secondary , Neoplasm Proteins/antagonists & inhibitors , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Skin Neoplasms/drug therapy , Skin Neoplasms/enzymology , Skin Neoplasms/radiotherapy , Stevens-Johnson Syndrome/drug therapy , Sulfonamides/therapeutic use , VemurafenibSubject(s)
Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/adverse effects , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/adverse effects , Desensitization, Immunologic/methods , Drug Hypersensitivity/therapy , Rhinitis/therapy , Urticaria/therapy , Adalimumab , Adult , Antibodies, Monoclonal, Humanized , Drug Hypersensitivity/immunology , Female , Humans , Psoriasis/drug therapy , Psoriasis/immunology , Rhinitis/immunology , Urticaria/immunologyABSTRACT
Los anticomiciales aromáticos, en especial, la fenitoína, pueden causar una reacción de hipersensibilidad típicamente caracterizada por sintomatología cutánea y sistémica variable (hepatopatía, adenopatías, mielotoxicidad, etc.), cuyo desenlace puede ser fatal en función de la precocidad diagnóstica, tiempo de uso del fármaco e intensidad de la afectación sistémica. Su incidencia oscila entre 1/1.000 y 1/10.000 exposiciones a esta sustancia y, habitualmente, comienza entre 1 y 3 meses después del inicio del agente causal. No se conoce a ciencia cierta su mecanismo de producción, aunque parecen implicados complejos procesos inmunopatogénicos. La supresión del medicamento y el tratamiento esteroide y antihistamínico suelen ser medi-das suficientes para la normalización clínico-analítica en un plazo de 4 a 10 semanas (AU)
Subject(s)
Male , Child , Humans , Carbamazepine/adverse effects , Drug Hypersensitivity/diagnosis , Pseudolymphoma/etiology , Anticonvulsants/adverse effectsABSTRACT
BACKGROUND: Toxic epidermal necrolysis (TEN) is a severe skin disorder characterized by separation of the dermal-epidermal junction, as is observed in second-degree superficial burns. It has been proposed that immunosuppressive treatment may improve prognosis of patients with TEN. METHODS: We report here a case series of patients with TEN treated with cyclosporin A (CSA) without other concomitant immunosuppressive agent. These patients (n = 11) were consecutively admitted to our Intensive Care Burn Unit because of severe TEN, involving a large body surface area (83 +/- 17% [mean +/- SD], median, 90%; range, 35-96%) and were treated with CSA 3 mg/kg per day enterally every 12 hours. We compared the series of patients treated with CSA with a historical series of patients admitted to our Intensive Care Burn Unit before CSA was introduced as part of the treatment protocol These patients (n = 6) were treated with cyclophosphamide (150 mg i.v. every 12 hours) and different doses of corticosteroids (> or =1 mg/kg per day of 6-methyl-prednisolone). Both groups of patients were similar in regard to age, delay from onset of disease to Intensive Care Burn Unit admission, and body surface area involved. RESULTS: Time from the onset of skin signs to arrest of the disease progression (1.4 +/- 0.3 days, vs. 3.6 +/- 1.5 days) and to complete reepithelialization (12.0 +/- 3.6 days, vs. 17.6 +/- 3.1 days) was significantly shorter in patients treated with CSA compared with those treated with cyclophosphamide and corticosteroids (p = 0.0002, and p = 0.0058, respectively). Significantly fewer patients in the CSA group had > or =4 organs failing (2 of 11 vs. 3 of 6, respectively, p = 0.029), had severe leukopenia (<1,000 cells/microL) (0 of 11 vs. 4 of 6, respectively, p = 0.006), or died (3 of 6 vs. 0 of 11, respectively, p = 0.0029). CONCLUSION: We conclude that immunosuppressive treatment with CSA is safe and is associated with a rapid reepithelialization rate and a low mortality rate in patients with severe TEN. Our data suggest that this regimen could be more effective than treatment with cyclophosphamide and corticosteroids. Prospective controlled trials are required to test the hypothesis that CSA is more effective than cyclophosphamide or other immunosuppressive regimens for the treatment of TEN.
Subject(s)
Cyclosporine/therapeutic use , Immunosuppressive Agents/therapeutic use , Stevens-Johnson Syndrome/drug therapy , Adult , Aged , Aged, 80 and over , Burns/drug therapy , Critical Care , Cyclophosphamide/adverse effects , Cyclophosphamide/therapeutic use , Cyclosporine/adverse effects , Drug Therapy, Combination , Female , Humans , Immunosuppressive Agents/adverse effects , Male , Methylprednisolone/adverse effects , Methylprednisolone/therapeutic use , Middle Aged , Treatment OutcomeABSTRACT
Trichilemmal keratosis (TK) is an uncommon epidermal tumor that exhibits a keratinizing surface with the formation of a cutaneous horn and that clinically resembles a hyperkeratotic actinic keratosis. Histologically, there is verrucous hyperplasia of the epidermis with orthokeratotic hyperkeratosis. TK is characterized by abrupt keratinization without formation of a granular cell layer, in the same manner as that in which the outer root sheath keratinizes (trichilemmal keratinization). The epidermis is acanthotic and contains pale-staining keratinocytes. Epithelial lobules and small trichilemmal cysts are connected to the thickened epidermis. We describe the clinical, histologic, and immunohistochemical findings of two cases of TK.
Subject(s)
Keratosis/pathology , Aged , Antigens, CD34/analysis , Female , Hair , Humans , Keratosis/immunologyABSTRACT
We report two new cases of ataxia-telangiectasia (A-T) in two child brothers. The first symptom of the disease was a serious and prolonged pellagra-like photodermatitis. This rare manifestation of the has not be reported before and it could be explain by a defect in DNA repair.
Subject(s)
Ataxia Telangiectasia/complications , Photosensitivity Disorders/etiology , Ataxia Telangiectasia/diagnosis , Ataxia Telangiectasia/genetics , Child , Diagnosis, Differential , Humans , Male , Photosensitivity Disorders/pathologyABSTRACT
We report a case, in a 74-year-old man, of chronic myelomonocytic leukemia (CMML) that showed cutaneous involvement in its terminal phase. The patient developed a nodular eruption with an irregular distribution over the entire skin surface. Histology showed an acute leukemic infiltration in the reticular dermis. We were able to demonstrate cells with intermediate myeloid and monocytic characteristics ("paramyeloid cells") in the skin biopsy and in bone marrow smears. There have been only four patients reported previously with similar clinical findings. In one of them the cutaneous eruption heralded an aggressive clinical shift of the disease, as in our case. The present case confirms the utility of skin biopsy in similar cases for predicting the evolution of the disease.
