sirolimus and Acne-Vulgaris

Several drugs have been associated with the development of eruptions that may simulate acne vulgaris. These drugs include corticosteroids, epidermal growth factor receptor inhibitors, cyclosporine, anticonvulsants, antipsychotics, antidepressants, tumor necrosis factor-alpha (TNF-alpha) inhibitors, anabolic steroids, danazol, antituberculosis drugs, quinidine, azathioprine and testosterone. In some cases, the eruption is clinically and histologically similar to acne vulgaris while, in other cases, the eruption is clinically suggestive of acne vulgaris without any histologic information. Additionally, in other cases of drug-associated acneiform eruptions, despite clinical similarity, histologic features are not consistent with acne vulgaris.

Topics: Acne Vulgaris; Acneiform Eruptions; Adrenal Cortex Hormones; Cyclosporine; Dactinomycin; ErbB Receptors; Humans; Lithium Carbonate; Sirolimus; Tumor Necrosis Factor-alpha

Rapalogs are emerging as promising targeted anticancer drugs. Activation of the PI3K/Akt/mTOR pathway has been observed in 15-50% of hepatocellular carcinomas.. In this phase II study, patients with advanced hepatocellular carcinoma and underlying cirrhosis received sirolimus (20 mg/week for 1 month then 30 mg/week). Tumour response was assessed every 8 weeks. The primary endpoint was the objective tumour response rate according to the Response Evaluation Criteria in Solid Tumours criteria. Secondary endpoints included the objective response according to the modified Response Evaluation Criteria in Solid Tumours criteria, safety, and pharmacokinetic parameters.. Twenty-five patients received sirolimus for a median of 20.6 weeks. Two patients had an objective response (8%, 95CI: 0.98-26.03), including one complete response, and 8 patients had stable disease. There were 2 cases of grade 5 toxicity (infections) and 5 cases of grade 3 toxicity. The main grade 1/2 toxicity was mild transient fatigue (76%). Median time to radiological progression and overall survival were 15.3 weeks (range: 8.2-173.9) and 26.4 weeks (range: 8.2-173.9) respectively. Use of the modified Response Evaluation Criteria in Solid Tumours criteria did not identify any further responders.. These data suggest that first-line sirolimus shows antitumoural efficacy in advanced hepatocellular carcinoma. Larger trials with Child A patients are needed.

Topics: Acne Vulgaris; Adult; Aged; Carcinoma, Hepatocellular; Disease Progression; Epistaxis; Fatigue; Female; Humans; Immunosuppressive Agents; Infections; Kaplan-Meier Estimate; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Mucositis; Multimodal Imaging; Positron-Emission Tomography; Sirolimus; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Treatment Outcome

De novo sirolimus in calcineurin inhibitor-free regimens, although potentially useful to improve early renal function, are complicated by various drug-related side effects.. We report a prospective open-label, multicenter, randomized trial to evaluate early conversion from a CsA-based to a sirolimus (SRL)-based regimen 10 to 24 days after renal transplantation. Of the 196 patients, 141 patients with a low-to-moderate immunological risk were eligible to be converted to SRL or to continue CsA. All patients received antithymocyte globulin-F single-bolus induction, mycophenolate mofetil, and steroids.. The primary endpoint, renal function determined by S-creatinine and estimated glomerular filtration rate calculated by Nankivell formula at 12 months was significantly better in the SRL group (1.51+/-0.59 vs. 1.87+/-0.98 mg/dL or 64.5+/-25.2 vs. 53.4+/-18.0 mL/min/1.73 m). Patient survival, graft survival, and incidence of biopsy-proven acute rejection after conversion were not statistically different. Drug discontinuations were significantly higher in the SRL group (36.2% vs. 19.7%). Significantly, more patients in the SRL group reported acne, aphtous, and temporary hyperlipidemia, whereas cytomegalovirus viremia was significantly decreased (7.3% vs. 28.2%).. Early conversion to a calcineurin inhibitor-free regimen with SRL in combination with mycophenolate mofetil may be a useful strategy to improve renal function. The identification of appropriate candidates and safe management of SRL-related adverse events will be a key to avoid the high rate of dropouts, which currently limit the broad applicability of this protocol.

Topics: Acne Vulgaris; Adrenal Cortex Hormones; Adult; Antilymphocyte Serum; Calcineurin Inhibitors; Creatinine; Drug Therapy, Combination; Female; Follow-Up Studies; Glomerular Filtration Rate; Graft Survival; Humans; Hyperlipidemias; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Patient Selection; Prospective Studies; Safety; Sirolimus; Time Factors; Tissue Donors

Sirolimus improves post transplant maintenance therapy in LTX. Dermal side effects causing pain and discomfort can limit patients' compliance. The package insert mentions such skin disorders as acne and rash. One case of sirolimus-induced leucocytoclastic vasculitis is reported in the literature.. From July 1998 to October 2003, Sirolimus was implemented in the immunosuppressive protocol in 23 out of 60 liver recipients. Sirolimus target levels are between 3 and <10 ng/dl. Combination with a calcineurinblocker and/or MMF (mycophenolate mofetil) depending on liver function and creatinine is standard. Weekly patient monitoring in the first month after discharge included physical examination, blood samples and immunosuppresant trough levels. Biopsies were taken from untypical efflorescences.. Three patients with non-specific effloresces were reported: one with leucocytoclastic vasculitis and one with exfoliate forearm dermatitis required change of medication while one perivascular lymphocytic eosinophilic dermatitis subsided after dose reduction. In three cases of mouth ulcer, trough levels exceeded 10 ng/dl and in six patients acne diminished after dose reduction. Eighteen out of 23 patients are still receiving sirolimus. Reasons for removal from the study were incompliance and incompatibility. Two patients died.. Immunosuppressants inevitably produce side effects in TX recipients. The positive management of troublesome side effects contributes importantly to compliance and patient survival.

Topics: Acne Vulgaris; Adult; Aged; Dermatitis, Exfoliative; Drug Eruptions; Female; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Oral Ulcer; Sirolimus; Vasculitis, Leukocytoclastic, Cutaneous

Autophagy is a catabolic process for eliminating damaged organelles or proteins to maintain cellular homeostasis. Recently, lipids have been demonstrated to be targets for autophagosomal degradation. Therefore, autophagy might be involved in sebaceous gland homeostasis, however, relevant data are lacking.. We investigated the role of autophagy in sebaceous lipogenesis and its regulatory mechanisms in human SZ95 sebocytes. We also examined the possible role of autophagy in 13-cis-retinoic acid (13-cis-RA)-mediated sebosuppression.. Autophagy markers expression was examined by immunohistochemistry in normal and acne lesional skin. SZ95 sebocytes were treated with autophagy inhibitors under starvation or treated with a combination of testosterone and linoleic acid (testosterone/LA), with or without autophagy inducer rapamycin or 13-cis-RA. Lipids were assessed by BODIPY and quantitative Nile Red staining. Autophagy-related gene 7 small interference RNA was used to confirm the role of autophagy on the sebosuppressive effect of rapamycin or 13-cis-RA.. Autophagy markers were strongly expressed in the maturing sebaceous gland cells in healthy skin, whereas downregulated in the acne-involved sebaceous glands. Testosterone/LA or insulin-like growth factor-1 inhibited starvation-induced sebocyte autophagy. Pharmacological inhibition of autophagy led to increased sebaceous lipid accumulation. Contrary, rapamycin inhibited the testosterone/LA-induced lipogenesis and expression of fatty acid synthesis genes via activating the autophagy pathway. 13-cis-RA increased autophagy in SZ95 sebocytes, partly via FoxO1 activation, and inhibition of autophagy abolished the sebosuppressive effect of 13-cis-RA.. Autophagy plays an important role in the modulation of lipogenesis in human sebocytes and is involved in the sebostatic effect of 13-cis-RA.

Topics: Acne Vulgaris; Autophagy; Cell Line; Humans; Isotretinoin; Lipogenesis; Sebaceous Glands; Sirolimus

Oral mechanistic target of rapamycin inhibitors have been shown to reduce visceral tumor volume in patients with tuberous sclerosis complex (TSC).. We sought to evaluate the cutaneous response to oral sirolimus in patients with TSC and an indication for systemic treatment, including long-term effects.. A retrospective analysis of 14 adult patients with TSC prescribed sirolimus to treat lymphangioleiomyomatosis was performed. Serial photographs of angiofibromas, shagreen patches, and ungual fibromas taken before, during, and after the treatment period were blinded, then assessed using the Physician Global Assessment of Clinical Condition (PGA). Microscopic and molecular studies were performed on skin tumors harvested before and during treatment.. Sirolimus significantly improved angiofibromas (median treatment duration 12 months; median PGA score 4.5 [range 1.5-5]; Wilcoxon signed rank test, P = .018) and shagreen patches (median treatment duration 10 months; median PGA score 4.5 [range 3.5-5]; Wilcoxon signed rank test, P = .039), whereas ungual fibromas improved in some patients (median treatment duration 6.5 months; median PGA score 4.66 [range 2.75-5]; Wilcoxon signed rank test, P = .109). Clinical, immunohistochemical, or molecular evidence of resistance was not observed (range 5-64 months of treatment).. This was a retrospective analysis limited to adult women with lymphangioleiomyomatosis.. Oral sirolimus is an effective long-term therapy for TSC skin tumors, particularly angiofibromas, in patients for whom systemic treatment is indicated.

Topics: Acne Vulgaris; Administration, Oral; Adult; Antibiotics, Antineoplastic; Drug Administration Schedule; Female; Humans; Middle Aged; Oral Ulcer; Retrospective Studies; Ribosomal Protein S6; Sirolimus; Skin Neoplasms; Treatment Outcome; Tuberous Sclerosis

Topics: Acne Vulgaris; Alopecia; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Azasteroids; Cantharidin; Cetuximab; Dutasteride; Female; Humans; Male; Molluscum Contagiosum; Sirolimus

We evaluated the clinical characteristics of sirolimus-induced acne in 80 recipients of renal transplantation. It developed in 36 of 48 (75%) men and 2 of 32 (6%) women. Lesion locations and clinical, bacteriologic, and histologic features differentiated sirolimus-induced acne from acne vulgaris, but therapeutic management was similar. The main limitation for this study was the absence of a control group without sirolimus. Epidermal growth factor inhibition by sirolimus is a plausible explanation for this acne.

Topics: Acne Vulgaris; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Sirolimus

Topics: Acne Vulgaris; Everolimus; Graft Rejection; Humans; Immunosuppressive Agents; Organ Transplantation; Sirolimus; United States; United States Food and Drug Administration