tacrolimus and Dermatomycoses

Dematiaceous molds are increasingly recognized as important human pathogens. We report 2 cases of cutaneous phaeohyphomycosis in renal allograft recipients, caused by Alternaria alternata and Curvularia spp., respectively, which demonstrate the diversity in clinical presentation, the different therapeutic strategies, and the clinical importance of azole antifungal-induced drug-drug interactions with immunosuppressive therapy.

Topics: Aged; Alternaria; Antifungal Agents; Ascomycota; Azoles; Dermatomycoses; Drug Interactions; Drug Therapy, Combination; Female; Hand Dermatoses; Humans; Immunocompromised Host; Immunosuppression Therapy; Kidney Transplantation; Leg Dermatoses; Male; Middle Aged; Opportunistic Infections; Tacrolimus

Topics: Antifungal Agents; Azoles; China; Dermatomycoses; Folliculitis; Humans; Lipase; Malassezia; Microbial Sensitivity Tests; Molecular Epidemiology; Skin; Tacrolimus; Terbinafine; Tinea Versicolor

Skin lesions are very common among organ transplant recipients (OTR), particularly infections and tumors, because of the immunosuppressive state these patients are put in.. 177 OTR were examined. Skin lesions were categorized into neoplastic, infectious, and inflammatory diseases.. The mean age of OTR was 52 years, the mean age at transplantation was 42.7 years, and kidney was the most common organ transplanted (72%). Skin lesions were found in 147 patients (83%). Cutaneous infections were seen in 106 patients (60%). Warts (30%) had the larger incidence and were associated with azathioprine (P = 0.026), cyclosporine (P = 0.006), and tacrolimus (P = 0.009). Superficial mycoses occurred in 16% of OTR, mostly onychomycosis, which was associated with tacrolimus (P = 0.040). Actinic keratosis (AK) occurred in 31% of patients and cutaneous tumors in 56%. Squamous cell carcinoma (SCC) was the most common tumor type affecting 36% of OTR (n = 64), with invasive SCC predominating over in situ SCC, whereas basal cell carcinoma (BCC) accounted for 17%. Both SCC and BCC were more numerous in patients' skin type I (P < 0.05). SCC was more frequent (36%) in combined kidney and liver recipients (P = 0.004), and BCC was associated with cyclosporine (P = 0.047). Inflammatory complications (acne, alopecia, hypertrichosis, and gingival overgrowth) were observed in 17.5% of patients.. Organ transplant recipients must be regularly evaluated by dermatologists, who should be alert to the onset of infections and skin (pre)malignant diseases in these patients.

Topics: Adolescent; Adult; Aged; Azathioprine; Brazil; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Child; Cyclosporine; Dermatomycoses; Female; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Keratosis, Actinic; Male; Middle Aged; Organ Transplantation; Risk Factors; Skin Diseases, Infectious; Skin Neoplasms; Tacrolimus; Warts; Young Adult

Topics: Aged; Amputation, Surgical; Combined Modality Therapy; Debridement; Dermatomycoses; Fatal Outcome; Humans; Immunocompromised Host; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Male; Mycophenolic Acid; Piperacillin; Postoperative Complications; Prednisone; Scedosporium; Tacrolimus; Tazobactam

To compare the in vitro interactions between tacrolimus (TAC)/triamcinolone acetonide (TRI) with itraconazole (ITC), terbinafine (TRB), bifonazole (BIZ), and amorolfine (AMF) in 28 clinical dermatophyte isolates, including 13 Trichophyton rubrum, 6 Trichophyton mentagrophytes, 5 Microsporum canis, and 4 Epidermophyton floccosum strains.. The interactions between TAC or TRI with antifungal agents were tested according to the microdilution checkerboard technique adapted from the CLSI M38-A2 microdilution method.. TAC and TRI did not exhibit significant antifungal activity against the tested strains at the highest concentration (MICs>8μg/mL). However, a strong synergistic interaction was observed for combinations of TAC with ITC (53%), TRB (53%), or BIZ (63%) against Trichophyton strains. Comparatively, TRI/ITC (11%) and TRI/BIZ (16%) combinations showed weaker synergistic activity against the same Trichophyton strains. TAC also showed synergistic interaction with ITC against 20% M. canis strains, with TRB against 60% M. canis strains, and with BIZ against 25% E. floccosum strains. No synergism was observed when M. canis and E. floccosum strains were exposed to TRI in combination with these drugs. Antagonism was not observed for any combinations.. Compared with TRI, TAC showed better synergy when combined with antifungal agents, especially topical TRB and BIZ, against dermatophyte isolates.

Topics: Antifungal Agents; Arthrodermataceae; Dermatomycoses; Drug Synergism; Humans; Imidazoles; Immunosuppressive Agents; Itraconazole; Microbial Sensitivity Tests; Morpholines; Species Specificity; Tacrolimus; Terbinafine; Triamcinolone Acetonide

The genus

Topics: Animals; Antifungal Agents; Calcineurin Inhibitors; Dermatomycoses; Fungal Proteins; Humans; Immunosuppressive Agents; Malassezia; Models, Molecular; Signal Transduction; Tacrolimus; Tacrolimus Binding Protein 1A

We present a case report of a patient with diffuse skin and systemic Kaposi's sarcoma (KS), 1 year after renal transplantation. A concomitant Pyrenochaeta romeroi granuloma of the right hallux was diagnosed and illustrated an important immunodysfunction in our patient. Four months after reduction in immunosuppression and switch to everolimus, a total regression of the KS was observed. Reduction in the immunosuppression and treatment with terbinafine cleared the P. romeroi infection, while lowering immunosuppression and changing the type of immunosuppressive therapy were important steps in the successful management of the KS. In recent years, evidence of the antitumor effects of everolimus is increasing: total regression of KS in combination with renal function preservation in renal graft recipients is possible with mammalian target of rapamycin (mTOR) inhibitor-based regimens. In addition, with increasing numbers of human immunodeficiency virus-positive transplant recipients, mTOR inhibitors may play a more crucial role in the management of KS.

Topics: Adult; Dermatomycoses; Drug Substitution; Everolimus; Female; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Liver Neoplasms; Mycophenolic Acid; Sarcoma, Kaposi; Skin Neoplasms; Tacrolimus; Treatment Outcome

To investigate the efficacy and mechanism of tacrolimus(FK506), which is a novel macrolide immunosuppressant, in inhibiting triggering receptor expressed on myeloid cells-1 (TREM-1) expression in a murine keratitis model induced by Aspergillus fumigatus.. TREM-1 was detected in 11 fungus-infected human corneas by quantitative real-time PCR (qRT-PCR). RAW264.7 macrophages were divided into four groups, which received treatment with zymosan (100 µg/ml), zymosan (100 µg/ml) + mTREM-1/Fc protein (1 µg/ml), or zymosan (100 µg/ml) + FK506 (20 µM) or negative-control treatment. After this treatment, the expression of TREM-1, interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) was assayed using qRT-PCR and ELISA. The mouse model of fungal keratitis was created by intrastromal injection with Aspergillus fumigatus, and the mice were divided into 2 groups: group A received vehicle eye drops 4 times each day, and group B received 4 doses of FK506 eye drops each day. Corneal damage was evaluated by clinical scoring and histologic examination,and myeloperoxidase (MPO) protein levels were also detected by ELISA. The expression of TREM-1, IL-1β and TNFα was then determined at different time points using qRT-PCR and ELISA.. TREM-1 expression dramatically increased in the human corneas with fungal keratitis. In contrast, FK506 reduced the expression of TREM-1, IL-1β and TNFα in RAW264.7 macrophages stimulated with zymosan. In the mouse model, at day 1 post-infection, the corneal score of the FK506-treated group was lower than that of the control, and polymorphonuclear neutrophil (PMN) infiltration was diminished. TREM-1, IL-1β and TNFα expression was significantly reduced at the same time point. However, the statistically significant differences in cytokine expression, clinical scores and infiltration disappeared at 5 days post-infection.. FK506 may inhibit the inflammation induced by fungi and alleviate the severity of corneal damage at an early stage of fungal keratitis by downregulating TREM-1 expression.

Topics: Animals; Aspergillus fumigatus; Cell Line; Cornea; Dermatomycoses; Humans; Immunosuppressive Agents; Membrane Glycoproteins; Mice; Receptors, Immunologic; Tacrolimus; Triggering Receptor Expressed on Myeloid Cells-1

A 3-year-old, neutered male Persian cat with chronic ulcerative facial dermatitis was diagnosed with feline idiopathic facial dermatitis based on signalment, clinical history and diagnostic test results, including dermatohistopathological evaluation. Initial treatment started with 4 weeks of oral antifungal/antibiotic medication for severe secondary infectious dermatitis of Malassezia and bacteria. As the lesions gradually improved, the oral medication was withdrawn, leaving only 0.1% topical FK506 (tacrolimus) ointment for the remaining lesions. Topical treatment was administered just in case any new lesions developed. The patient has been managed effectively with topical tacrolimus and no side-effects were observed during treatment. Feline idiopathic facial dermatitis is known as a difficult dermatosis to manage successfully, but our experience suggests that it may respond to topical tacrolimus.

Topics: Administration, Topical; Animals; Antifungal Agents; Cat Diseases; Cats; Dermatomycoses; Immunosuppressive Agents; Malassezia; Male; Tacrolimus

Topics: Alternaria; Ankle; Dermatomycoses; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Itraconazole; Kidney Transplantation; Middle Aged; Pyrimidines; Retreatment; Tacrolimus; Triazoles; Voriconazole

Tacrolimus, an immunosuppressant used in organ transplant surgery, is inhibitory to some medically important fungi but also may obstruct azole monotherapy in the immunocompromised patient. We observed a case of cutaneous phaeohyphomycosis caused by Alternaria alternata in a liver transplant recipient who had been under tacrolimus immunosuppression for 6 months post-transplantation. At the onset of the infection, the patient presented with an increased whole-blood tacrolimus level. After a simple surgical excision the patient was discharged from the hospital without antifungal treatment but with an adjusted tacrolimus dosage. Literature review on fungal infections in patients receiving tacrolimus suggested these patients experience cutaneous and deep mould infections that are more frequent, severe and therapy-refractory than those seen in patients with other types of immunosuppression.

Topics: Aged; Alternaria; Dermatomycoses; DNA, Ribosomal Spacer; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Sequence Analysis, DNA; Tacrolimus

Deep dermatophytosis and nocardiosis are uncommon infections. This article describes a patient who was immunosuppressed with deep dermatophytosis caused by Trichophyton rubrum and concurrent disseminated nocardiosis. The infections occurred 16 years after the patient underwent renal transplantation, and may have been related to tacrolimus therapy.

Topics: Dermatomycoses; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Nocardia asteroides; Nocardia Infections; Opportunistic Infections; Tacrolimus; Trichophyton

Topics: Administration, Cutaneous; Dermatomycoses; Diagnosis, Differential; Facial Dermatoses; Humans; Immunosuppressive Agents; Male; Middle Aged; Psoriasis; Tacrolimus

Scopulariopsis brevicaulis is a causal agent of onchomycosis. We report the unusual clinical manifestations caused by this opportunist fungus.. A 61-year-old man consulted in February 1997 for a budding lesion located on the right medial malleolus. This patient had had a liver transplantation for primary biliary cirrhosis in 1990 and had been taking prednisone and cyclosporine since this time. Cyclosporine had been recently replaced by tacrolimus. The histology examination of a lesion specimen taken from the ankle evidenced a dermal mycosis due to opportunist filamentous fungus. Total excision was performed. The patient then developed nodular lesions of the left elbow during the summer of 1997. Mycology culture of a skin biopsy grew numerous colonies of Scopulariopsis brevicaulis. Excision of the elbow lesion was delayed due to hospitalization for suspected graft rejection and development of insulin-dependent diabetes. The elbow lesion was then resected followed by a skin graft. The mycology examination identified the same causal agent.. This liver transplant recipient developed two unusual extra-ungual localizations (ankle and elbow) of a Scopulariopsis brevicaulis infection. Chronic immunosuppression favored development of the infection with a pseudo-epithéliomatous presentation. The histology and mycology examinations were necessary for positive diagnosis.

Topics: Biopsy; Cyclosporine; Dermatomycoses; Humans; Immunocompromised Host; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Mitosporic Fungi; Opportunistic Infections; Prednisone; Tacrolimus

Topics: Dermatomycoses; Granuloma; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Postoperative Complications; Tacrolimus