isotretinoin and Necrosis

Isotretinoin is a retinoic acid frequently used in monotherapy or combined with narrow-band ultraviolet B (NBUVB) irradiation to treat patients with acne and psoriasis vulgaris. As both diseases need frequent and/or prolonged therapeutic interventions, the study of the genotoxicity of retinoids becomes important. Our aim was to study the genotoxic effects of isotretinoin alone or combined with NBUVB. In vitro studies were performed in the absence of S9 metabolic activation using blood from five healthy volunteers, incubated 72 h with isotretinoin (1.2-20 μM) (i.e., at concentrations usually achieved in blood with therapeutic doses as well as at higher concentrations). In vivo studies were also performed using blood from two patients with acne and three patients with psoriasis vulgaris treated with isotretinoin in monotherapy (8 or 20mg/day) or combined with NBUVB (20mg isotretinoin/day+NBUVB). The genotoxic effect was evaluated by the cytokinesis-blocked micronucleus and the comet assays. Our studies showed that isotretinoin alone was not genotoxic when tested in human lymphocytes in vitro and in vivo. There was no clear genotoxic effect in psoriatic patients treated with isotretinoin and NBUVB. The in vitro studies showed that isotretinoin induced apoptosis and necrosis in human lymphocytes at higher doses.

Topics: Acne Vulgaris; Adult; Apoptosis; Cells, Cultured; Combined Modality Therapy; Comet Assay; Cytokinesis; Dermatologic Agents; Female; Humans; Isotretinoin; Lymphocytes; Male; Micronucleus Tests; Necrosis; Psoriasis; Ultraviolet Rays

Twenty-five patients with metastatic malignant melanoma were treated with isotretinoin (13-cis-retinoic acid) orally at 1 mg/kg daily and recombinant interferon alfa-2a (INF-alpha) subcutaneously at 3 million units daily for 16-48 weeks. Therapy was well tolerated; fatigue and hyperlipidemia were the most frequent dose-limiting toxicity and necessitated dose reductions in 14 patients. Two patients achieved a complete response, and 3 responded partially for a total response rate of 20% (95% confidence interval: 4-36%). Responses occurred primarily in patients with limited tumor burden and disease confined to the skin and lymph nodes. Significant elevations in peripheral blood 2'-5'-oligoadenylate synthetase activity and natural killer activity were observed with therapy. The magnitude of these changes, however, was not predictive of response. Biopsy specimens of two responding lesions showed extensive necrosis of tumor. One specimen showed large aggregates of melanophages in association with tumor. The combination of isotretinoin and IFN-alpha is an active, easily administered regimen with acceptable toxicity for metastatic malignant melanoma.

Topics: 2',5'-Oligoadenylate Synthetase; Adult; Aged; Antineoplastic Agents; Female; Humans; Interferon alpha-2; Interferon-alpha; Isotretinoin; Killer Cells, Natural; Lymph Nodes; Lymphatic Metastasis; Male; Melanoma; Middle Aged; Necrosis; Neoplasm Metastasis; Neoplasm Staging; Recombinant Proteins; Skin Neoplasms

Topics: Administration, Cutaneous; Adult; Drug Therapy, Combination; Facial Dermatoses; Female; Humans; Isotretinoin; Metronidazole; Necrosis; Prednisolone; Rosacea; Skin; Treatment Outcome

Background /Aim: Acne fulminans is a rare form of acne vulgaris with acute clinical deterioration including systemic signs. Etiopathogenesis and management remain largely unknown. Our aim is to assess the efficacy of a combined therapeutic regimen of systemic isotretinoin and prednisolone following the recent concepts of acne pathogenesis and drug kinetics.. A prospective case series was recruited over 15 years. Isotretinoin 0.5 mg/kg bw/d (0.25-0-0.25) and prednisolone 30 mg/d (10-10-10) were administered concomitantly with prednisolone being tapered after that time. The overall efficacy was evaluated at month 1 and every month thereafter. Daily drug doses were split to reduce the risk for adverse effects.. 26 patients (20 male, 77%) at a mean age of 19 years and a history of acne vulgaris of 3.2 years presented acutely necrotic and ulcerating skin papules (100%), fever (45%), arthralgia (38.5%), leukocytosis (88.5%) and elevated erythrocyte sedimentation rate (100%). After one month of treatment resolution of systemic signs was achieved in all patients and a >50% skin lesion improvement in 17 patients (65%).. The concomitant administration of isotretinoin (0.5 mg/kg bw/d, 0.25-0-0.25) and prednisolone 30 mg/d (10-10-10) is able to resolve systemic signs and markedly improve skin lesions in 65% of the patients at one month.

Topics: Acne Vulgaris; Adolescent; Adult; Arthralgia; Drug Therapy, Combination; Female; Fever; Humans; Isotretinoin; Leukocytosis; Male; Necrosis; Prednisolone; Prospective Studies; Skin; Skin Ulcer; Young Adult

Isotretinoin is considered to be a safe and effective therapy in otherwise therapy-resistant acne. Elevated serum creatine phosphokinase values with or without muscle-related symptoms in isotretinoin-treated patients have been reported and interpreted as benign phenomena, lethal cases have not been described yet. We present the case of a 20-year-old male who died from severe generalised rhabdomyolysis associated with isotretinoin treatment.

Topics: Acne Vulgaris; Administration, Oral; Administration, Topical; Dermatologic Agents; Dose-Response Relationship, Drug; Drug Substitution; Fatal Outcome; Humans; Isotretinoin; Long-Term Care; Lung; Male; Muscle, Skeletal; Necrosis; Phagocytosis; Pulmonary Edema; Rhabdomyolysis; Ventricular Fibrillation; Young Adult

We report a case of severe "bodybuilding acne" in a 22-year-old patient. Treatment with isotretinoin paradoxically led to exaceibation and occurrence of pyogenic granuloma-like lesions.

Topics: Acne Vulgaris; Adult; Anabolic Agents; Androgens; Anti-Bacterial Agents; Causality; Cefotiam; Dermatologic Agents; Granulation Tissue; Granuloma, Pyogenic; Humans; Inflammation; Isotretinoin; Male; Necrosis; Suppuration; Testosterone; Weight Lifting

Acne fulminans is a syndrome of fulminant, necrotizing acne associated with bone lesions, constitutional symptoms, and laboratory abnormalities. A case report of an adolescent male with acne fulminans following withdrawal of isotretinoin and prednisone is presented.

Topics: Acne Vulgaris; Adolescent; Humans; Isotretinoin; Male; Necrosis; Skin; Withholding Treatment

Treatment of rat C6 glioma with high doses of 13 cis-retinoic acid (cRA) was responsible for death related to haemorrhagic necrosis localized to the tumor. Our aim was to explore this adverse effect of retinoid treatment. We show that cRA-treated C6 glioma at 25 mg/kg/day for 18 days exhibits in vivo an increase T-PA activity, which is responsible for a localized tumor fibrinolytic activity. Production of t-PA is supported by specific enhancement of gene expression, as was shown by the increase in t-PA mRNA (x 2.3). This production is a direct effect of cRA when treating the tumor, since tumor cells themselves do not produce enough t-PA and treatment of control rats does not increase the t-PA level. T-PA production by rat C6 glioma is in vivo related to the specific synthesis of t-PA by the C6 cell-line. The stimulation of C6 cell-line by cRA in vitro is dose-dependent and reached a maximum for 3 and 30 microM at the 72nd h. So cRA-treated C6 glioma cells produce t-PA which appears to be the major species associated with the fibrinolytic activity-induced intra-tumoral haemorrhage after exposure to retinoid treatment.

Topics: Animals; Antineoplastic Agents; Brain Neoplasms; Cerebral Hemorrhage; Death, Sudden; Drug Screening Assays, Antitumor; Female; Fibrinolysis; Gene Expression Regulation, Neoplastic; Glioma; Isotretinoin; Necrosis; Neoplasm Proteins; Neoplasm Transplantation; Rats; Rats, Sprague-Dawley; RNA, Messenger; RNA, Neoplasm; Tissue Plasminogen Activator; Tumor Cells, Cultured

A patient with glioblastoma multiforme (GBM) who had failed conventional therapy was treated with IL-2 gene therapy. The patient received 10 subcutaneous immunizations with autologous tumor cells and fibroblasts genetically modified to secrete IL-2 by retroviral gene transfer. An antitumor immune response mediated in part by CD8+ cytotoxic T cells was demonstrated with the patient's peripheral blood mononuclear cells. A magnetic resonance imaging (MRI) scan performed 4 weeks after the highest treatment dose revealed marked tumor necrosis. These results support the evaluation of this form of IL-2 gene therapy in additional patients with glioblastoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cells, Cultured; Combined Modality Therapy; Fatal Outcome; Female; Fibroblasts; Genetic Therapy; Genetic Vectors; Glioblastoma; Humans; Injections, Subcutaneous; Interleukin-2; Isotretinoin; Lomustine; Magnetic Resonance Imaging; Middle Aged; Necrosis; Neoplasm Recurrence, Local; Neoplastic Stem Cells; Procarbazine; Radioimmunotherapy; Radiosurgery; Recombinant Fusion Proteins; Retroviridae; Salvage Therapy; T-Lymphocytes, Cytotoxic; Tamoxifen; Temporal Lobe; Transfection; Tumor Cells, Cultured; Vincristine

The present study was designed to investigate the effects of 13-cis-retinoic acid (13-cis-RA) (100 micrograms/mouse/day) and androgen ablation (castration) alone and in combination on growth of a human prostatic carcinoma line (LNCaP) transplanted to athymic nude mice as an experimental model. The results of these studies suggest that; (1) androgen ablation (castration) significantly decreased the size of LNCaP xenograft as compared to untreated animals; (2) when 13-cis-RA was administered to nude mice carrying established tumors (0.51 +/- 0.04 cm3), the tumor size was significantly reduced as compared to untreated controls (0.65 +/- 0.06 cm3 versus 1.63 +/- 0.12 cm3). About 50% of the animals in this group showed xenografts necrosis followed by complete regression of tumors by five months; (3) the combination of androgen ablation and 13-cis-RA treatment to nude mice carrying tumors showed synergistic effect in decreasing the tumor size. These results indicate that combination therapies based on androgen ablation and retinoid administration may be a useful approach for the treatment of prostate cancer.

Topics: Animals; Humans; Isotretinoin; Male; Mice; Mice, Nude; Necrosis; Neoplasm Transplantation; Orchiectomy; Prostatic Neoplasms; Tumor Cells, Cultured

Systemic use of retinoids is common in the treatment of various dermatological disorders. Blepharitis and conjunctivitis have been reported in 20-45% of the patients following systemic treatment with 13-cis-retinoic acid. Our purpose was to study the histopathological changes in the eyelids caused by long-term systemic treatment of female New Zealand rabbits with isotretinoin (2 mg/kg) and etretinate (2 mg/kg). The histopathological evaluation showed degenerative changes in the meibomian gland acini, leading to cell necrosis and a decrease in the basaloid cells lining the acini walls. No evidence of acute or chronic inflammatory reaction was noted.

Topics: Administration, Oral; Animals; Capsules; Etretinate; Eyelids; Female; Isotretinoin; Meibomian Glands; Necrosis; Rabbits

Topics: Acne Vulgaris; Adolescent; Cyclophosphamide; Granulomatosis with Polyangiitis; Humans; Isotretinoin; Lung; Male; Necrosis; Prednisone; Skin; Skin Ulcer; Tretinoin