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Open access

Wei-gang Cao and Bao-an Qiu

Abstract

Psoriasis is a chronic recurrent inflammatory dermatosis, which is characterized by epidermal proliferation and erythema scales. Its etiology and pathogenesis are still unknown and treatment is difficult. The concentration of tacrolimus for the treatment of psoriasis has not been reported at home and abroad. In this report, we detected the tacrolimus plasma concentration and hope to provide a certain reference value for the clinical treatment of psoriasis.

Open access

I. Balicki

Abstract

The objective of this study was to assess the treatment of chronic superficial keratitis (CSK) in dogs with the use of tacrolimus and DMSO.

The study was conducted on 16 dogs - 7 males and 9 females, aged 3 to 11 years, diagnosed with CSK. The disease was treated with ophthalmic drops containing 0.02% tacrolimus and 50% DMSO, administered to the ocular surface three times a day. Prior to the treatment and after 5 weeks of therapy, the corneal neovascularisation, pigmentation, and also the redness and depigmentation of the third eyelid margin were assessed. The percentage of the corneal surface afflicted with inflammatory processes was calculated on the basis of photographs taken with the use of IsoCalc.com’s Get Area software for Corel DRAW 12.

It was found that the application of tacrolimus and DMSO caused a reduction of inflammatory process and neovascularisation in the cornea. The mean corneal surface afflicted with inflammatory processes was statistically significantly reduced from 69.9% to 43.9% (p ≤ 0.01) - in case of the right corneas, and from 58.9% to 38.6% in case of the left corneas. Of 32 corneas diagnosed with the pigmentation, the reduction of the pigmentation was observed in 14, while in 16 the pigmentation increased.

The treatment of CSK with the use of tacrolimus and DMSO causes the reduction in terms of inflammatory processes and neovascularisation, but in many cases does not inhibit the progress of the pigmentation.

Open access

C.E. Vari, H. Suciu, Mihaela Ispas, S. Voidăzan and Daniela Lucia Muntean

Abstract

In a retrospective study, the safety profile and efficacy of immunosuppressive medication was evaluated in 35 patients with cardiac transplant in Targu Mures during 1999-2011 (11 treated with cyclosporine, 24 with tacrolimus, both drugs were associated with mycophenolate mofetil). Therapeutic benefit was measured by survival curve and lack of rejection while safety was evaluated by measuring plasma immunosuppressive drugs levels and evaluation of specific adverse events (nephrotoxicity, diabetes, and hypertension). The most frequent side effect was nephrotoxicity (significant reduction in glomerular filtration rate estimated by MDRD formula), but no significant differences were found between the 2 medications.

Open access

Nikolina Basic-Jukic, Lea Katalinic, Marijana Coric, Monika Kocman, Branimir Krtalic and Petar Kes

Abstract

Amiodarone is a potent inhibitor of CYP3A4 and can increase serum concentrations of drugs that are substrates of this enzyme system. Immunosuppressive drugs are also metabolized through the cytochrome metabolic pathway what may lead to important drug-drug interactions. A 60-year-old female received her second allograft from the deceased donor and was treated with tacrolimus, mycophenolate mofetil and steroids. Amiodarone was introduced for treatment of paroxysmal atrial fibrillation four days after the transplantation. One month after the discharge she was readmitted to hospital for evaluation of the creeping creatinine. Biopsy showed borderline acute rejection. She received 3 boluses of 6- methilprednisolone but creatinine continued to rise. Repeated biopsy was without signs of rejection with mild interstitial fibrosis/tubular atrophy, mild global glomerulosclerosis and moderate arterial sclerosis. However, tubular vacuolization was prominent. After careful revision of her therapy we decided to replace amiodarone with sotalol. One week later her creatinine fell from 350 to 220 μmol/l and remained stable. This case illustrates possible amiodarone nephrotoxicity in a renal transplant recipient. We suggest that patients who need amiodarone in combination with tacrolimus be closely monitored by both cardiologists and nephrologists, with frequent determinations of tacrolimus trough levels and serum creatinine measurements.

Open access

Nikolina Basic-Jukic, Ljubica Bubic-Filipi, Lea Katalinic and Judita Lelas

Abstract

Introduction. Tacrolimus extended-release formulation enables once-daily use. Although an increasing number of patients have been converted from twice-daily (Tac- BID) to once-daily (Tac-QD) formulation, the available information regarding the initiation and follow-up of Tac- QD is sparse. In the present study we investigated influence of switch from Tac-BID or cyclosporine to Tac-QD on renal allograf function, proteinuria and protein-creatinine (P/C) ratio. Methods. Between October 2012 and October 2014, the switch from Tac-BID or cyclosporine to tacrolimus extended-release formulation was done in 129(38% female, mean age 49 years) renal transplant recipients at different time after transplantation. The analysis focused on markers of graft function (GFR, serum creatinine, proteinuria, P/C ratio), liver function (AST, ALT, γGT, alkaline phosphatase) and blood glucose. Clinical data were obtained at baseline (before conversion), 1 month (V1), 6 months (V6) and 12 months (V12) after conversion. Results. Both serum creatinine and GFR showed a statistically significant improvement. With GFR, signifycant improvement was observed as early as V1 and it continued to increase throughout the study period up to V12 (all between-visit changes were statistically significant). With serum creatinine, mean levels were numerically decreasing throughout the follow-up period, but a significant improvement occurred at V6 and remained significant at V12 (both vs. V0 values). Proteinuria and P/C ratio did not show any significant change through the observation period. In the majority of patients, the baseline values of AST, ALT, GGT, AlP and glucose were within normal limits and did not change significantly through the observation period. Analysis of tacrolimus C0 showed a significant decrease throughout the follow-up period, at practically all visit. This finding was paralleled by a significant tacrolimus dose decrease from baseline to V6 and V12, as well as by a significant decrease of tacrolimus dose/body weight. Conclusions. Conversion from cyclosporine or Tac-BID to extended-release Tac-QD improves graft function in renal transplant recipients, without influence on proteinuria or P/C ratio.

Open access

Alexandra NG Hoi-Yan and Chi Chiu Mok

Abstract

The ultimate goal of treating rheumatic disease is to achieve rapid suppression of inflammation, while at the same time minimizing the toxicities from rheumatic drugs. Different patients have different individual pharmacokinetics that can affect the drug level. Moreover, different factors, such as renal function, age or even different underlying diseases, can affect the drug level. Therefore, giving the same dosage of drugs to different patients may result in different drug levels. This article will review the usefulness of therapeutic drug monitoring in maximizing drug efficacy, while reducing the risk of toxicities in Hydroxychloroquine, Mycophenolate Mofetil, Tacrolimus and Tumor Necrosis Factor inhibitors (TNF Inhibitors).

Open access

Suzana Nikolovska, Đorđi Gocev and Katerina Damevska

Abstract

Granuloma faciale is an uncommon inflammatory skin disorder clinically characterized by single or multiple, reddishbrown nodules or plaques primarily occurring on the face of middle-aged men. Occasionally, extra-facial involvement has been reported, usually on sun-exposed areas. Although the etiology is somewhat unclear, granuloma faciale is considered a localized form of chronic leukocytoclastic vasculitis with a prominent eosinophilic infiltrate and fibrosis in the later stages of the disease. Histological examination of lesions reveals a dense polymorphous inflammatory infiltrate that consists mainly of eosinophils and neutrophils separated from the epidermis by a narrow band zone with normal collagen, deprived of cells. Leukocytoclastic vasculitis is often seen. Clinical diagnosis is suspected in few cases, so definite diagnosis of granuloma faciale requires a biopsy. The disease is notoriously resistant to many therapies and often tends to relapse after treatment is discontinued.

We present a female patient with granuloma faciale on the back and on the tip of the nose, misdiagnosed clinically as basall cell carcinoma and granuloma annulare. Her original histological diagnosis, made by a pathologist, was pyogenic granuloma. After revision of histologic findings of the biopsy specimens, granuloma faciale was diagnosed by a dermatopathologist. The treatment with cryotherapy and topical steroids was unsuccessful. Improvement of lesions was observed after use of tacrolimus 0.1% ointment, but lesion recurred after discontinuation of treatment.

Open access

Đorđije Karadaglić

Abstract

Lichen sclerosus (LS) is a chronic inflammatory dermatosis localized mainly in the anogenital region, accompanied by itching, atrophy and sclerosis. Progressive destructive scarring in genital lichen sclerosus (GLS) may result in burying of the clitoris in females and phimosis in males. Affected persons have an increased risk of genital cancers. It is often unrecognized in everyday clinical practice due to undiagnosed squamous cell carcinoma at the site of lesions. Remissions are rare and the estimated remission rate is only 16%. GLS is a lifelong, incurable condition, but signifi cant improvement can be achieved. Numerous therapeutic modalities have been used in GLS; unfortunately, the number of controlled studies is small and the results are mostly related to the management of symptoms, not the progression of the disease and destructive scarring. A systemic meta analysis of seven randomized controlled trials on local therapy of GLS was performed. It included a total of 249 patients treated with six topical agents: clobetasol propionate, mometasone furoate, testosterone, dihydrotestosterone, progesterone and pimecrolimus. Topical corticosteroids, clobetasol propionate 0.05% (highly potent) and mometasone furoate 0.05% (potent), showed to be significantly more efficient compared to placebo. Pimecrolimus 1% cream and clobetasol propionate 0.05% showed similar efficacy. Both agents have proven effective in the treatment of GLS: there was no statistically significant difference in relieving symptoms of pruritus and burning/pain. Tacrolimus 0.1% ointment also proved to be effective in the treatment of GLS. Topical androgens and progesterone did not show significant efficacy. Topical tretinoin and calcipotriol have been used with limited success, but they may induce irritation, so they are rarely used in the treatment of GLS. Other therapeutic options for GLS include ultraviolet A1 (UVA-1) phototherapy, methotrexate, retinoids, cyclosporine, stanozolol, hydroxychloroquine, calcitriol, laser and photodynamic therapy, but the number of patients is small to allow for conclusive assessment. Surgery is not a standard therapeutic option for GLS.

In conclusion, treatment of GLS should be carried out in two phases: introduction of remission and maintenance of remission; topical therapy should include highly potent corticosteroids once daily during three months, followed by twice per week, or twice daily during 4 to 6 weeks, and then twice per week. There are different opinions regarding maintenance therapy: application of super potent or potent topical corticosteroids; these patients need long-term, several-year follow-up, although there is no agreement what parameters should be assessed; treatment efficacy is often reduced to monitoring GLS symptoms.

Open access

Natsuki Aoyama-Maeda, Taro Horino, Osamu Ichii and Yoshio Terada

Abstract

Macrophage activation syndrome (MAS), a variant of secondary hemophagocyticlymphohistiocytosis, is a potentially life-threatening complication of inflammatory and autoimmune diseases. We present a case of MAS as a rare manifestation of systemic lupus erythematosus. Although initial treatment with corticosteroid, with or without cyclosporine A, is justified in patients with MAS, evidence regarding the effectiveness of this treatment protocol remains to be clarified. Our patient was successfully treated with a combination of intravenous immunoglobulin therapy and intravenous methyl predonisolone pulse therapy, which was followed by a course of oral prednisolone and oral tacrolimus. Based on our experience, we propose tacrolimus to provide a more useful adjuvant treatment to corticosteroid therapy than cyclosporine A.

Open access

Kreetachon Veerakikosol, Pajaree Chariyavilaskul, Natavudh Townamchai and Supeecha Wittayalertpanya

Abstract

Background

Cytochrome P450 (CYP) 3A5 is a major isoform metabolizing tacrolimus. Individual variation in the metabolism may result from CYP3A5 single nucleotide polymorphisms (SNPs). CYP3A5*3 polymorphism is strongly associated with tacrolimus pharmacokinetic variations in 65%–85% of Asian populations. A minor polymorphism related to requirement for tacrolimus is the POR*28 mutation, which increases in vivo CYP3A activity for tacrolimus. These two SNPs might affect individual maintenance dosages of tacrolimus.

Objectives

To determine the association of CYP3A5*3 and POR*28 SNPs with maintenance dosage requirements for tacrolimus in Thai recipients of kidney transplants.

Methods

We enrolled 150 Thai recipients of kidney transplants. Clinical laboratory data were recorded 3 months after first administration of tacrolimus. Two SNPs; rs776746 A > G (CYP3A5*3 allele) and rs1057868 C > T (POR*28 allele) were assessed. All 300 genotypes were analyzed by real-time polymerase chain reactions.

Results

Recipients were classified into 9 groups according to possible matching genotypes. The mean dosage required for the maintenance phase was significantly higher in the CYP3A5*1 allele or CYP3A5 expressers (groups 1-6, 0.163, 0.167, 0.141, 0.128, 0.131, and 0.174 mg/kg/day, respectively) than those not expressing CYP3A5*3/*3 or CYP3A5 (groups 7-9, 0.081, 0.073, and 0.069 mg/kg/day, respectively, P < 0.05). When the mean dosage was compared under POR*28 one or two alleles in CYP3A5 expressers, P was significantly smaller than in CYP3A5 expressers with POR*1/*1.

Conclusions

CYP3A5 polymorphism is key to determining tacrolimus dosage requirements during the maintenance phase in kidney transplant recipients and POR*28 may contribute to the interindividual variability