tacrolimus and Ulcer

Vernal keratoconjunctivitis (VKC) is a chronic, bilateral corneal and conjunctival problem which typically presents in young individuals. VKC is characterized by itching, photophobia, white mucous discharge, lacrimation, foreign body sensation, and pain due to corneal involvement of shield ulcers. Vernal keratoconjunctivitis is categorized within ocular diseases. The diagnosis is clinical, as no sure biomarkers pathognomonic of the disease have yet been identified. The VKC therapy relies on different types of drugs, from antihistamines and topical steroids to cyclosporine or tacrolimus eye drops. In extremely rare cases, there is also the need for surgical treatment for the debridement of ulcers, as well as for advanced glaucoma and cataracts, caused by excessive prolonged use of steroid eye drops. We performed a systematic review of the literature, according to PRISMA guideline recommendations. We searched the PubMed database from January 2016 to June 2023. Search terms were Vernal, Vernal keratoconjunctivitis, and VKC. We initially identified 211 articles. After the screening process, 168 studies were eligible according to our criteria and were included in the review. In this study, we performed a systematic literature review to provide a comprehensive overview of currently available diagnostic methods, management of VKC, and its treatments.

Topics: Conjunctivitis, Allergic; Cyclosporine; Humans; Ophthalmic Solutions; Tacrolimus; Ulcer

Recurrent and painful genital ulcers are the hallmark of Behçet's disease.. To determine the efficacy of pimecrolimus (PIM) cream on the pain and healing time of genital ulcers.. A total of 76 patients were randomized to either receive PIM cream plus colchicine (COL) tablets (1-2 g/day) or COL tablets (1-2 g/day) alone for 1 month. Clinical evaluations were performed in 68 patients at the baseline and on the 3rd, 7th, 10th, 14th and 28th days of treatment. Also, genital ulcer pain was evaluated using a verbal pain score at each visit. Safety was monitored through adverse event reporting and laboratory tests.. The mean healing time of genital ulcers was shorter in the PIM + COL group (4.2 +/- 1.5 days) than the COL group (4.7 +/- 1.8 days), without statistical significance (p = 0.399). Visual analog scale scores decreased in both groups significantly. Neither of the treatment modalities was found to be superior to the other; however, pain was relieved in 4.2 +/- 0.5 days in PIM + COL group and in 5.5 +/- 1.2 days in COL group in the intention to treat population (p = 0.023). Observed adverse events were transient.. Compared to COL alone, COL + PIM cream shortens the pain duration without any significant effect on healing time.

Topics: Adult; Behcet Syndrome; Colchicine; Dermatologic Agents; Drug Therapy, Combination; Emollients; Female; Genital Diseases, Female; Genital Diseases, Male; Humans; Male; Pain; Pain Measurement; Retrospective Studies; Scrotum; Tablets; Tacrolimus; Treatment Outcome; Turkey; Ulcer; Vagina

Topics: Gastrointestinal Diseases; Humans; Immunosuppressive Agents; Kidney Transplantation; Tacrolimus; Transplant Recipients; Ulcer

A 36-year-old male was admitted to our hospital with diarrhea, weakness and loss of appetite over two months. He had received a liver transplant two years before and was taking immunosuppressors (everolimus, mycophenolate mofetil and tacrolimus). Initial laboratory tests showed iron-deficiency anemia (Hb 9.8 g/dl), lymphopenia and mild elevation in C-reactive protein (35 mg/l). Blood and stool cultures, and cytomegalovirus (CMV) quantitation in blood were all negative. Finally, the colonoscopy showed two rectal fimbriated ulcers close to the anal sphincter and multiple biopsies from the ulcer margins identified the presence of Epstein-Barr virus (EBV). All symptoms were completely resolved three weeks after immunosuppression was diminished. He underwent a follow-up colonoscopy, without any evidence of the former ulcers.

Topics: Adult; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Humans; Immunosuppressive Agents; Liver; Male; Tacrolimus; Ulcer

Dear Editor, cutaneous chronic graft versus host disease (cGVHD) is a pathological process consisting of donor-derived T-cells aimed at the antigens of the recipient. It exhibits a large range of clinical presentations resembling morphea and deep sclerosis/fasciitis, all characterized by both inflammation and progressive dermal and hypodermic fibrosis (1). Although classic scleroderma-like lesions in cGVHD are nummular or irregular plaques and linear bundles associated with hypo- or hyperpigmentation (2), we report an atypical case with ulcerative presentation. No other case-reports of morphea-like or scleroderma-like cGVHD with an ulcerated appearance after liver transplantation (LT) and magnetic resonance imaging (MRI) correlation have been found in the literature. CASE REPORT Ten months after LT due to an end-stage cirrhosis associated with multifocal hepatocarcinoma (HCC), a 61-year-old man on immunosuppressive therapy with Tacrolimus (1 mg) and Everolimus (10 mg) presented to our clinic for a skin lesion in the right scapular region. We observed a flat ulcerated plaque with areas of sclerosis, minimal necrosis, and well-defined slightly erythematous margins (Figure 1, a). On palpation, the plaque had a hard consistency and was slightly painful. The skin lesion had been preceded by subjective discomfort with stinging sensation for seven months before its onset. Gradually lesion developed starting from a small, flat, oval purplish plaque associated with a progressive increase in pain. Patient denied dysphagia, retrosternal heartburn, Raynaud's phenomenon, arthralgia, and dyspnea. A previous MRI (Figure 2, a,b) showed subcutaneous and muscle edema. Blood tests showed abnormal liver function indexes due to extrahepatic cholestasis, while C-reactive protein, erythrocyte sedimentation rate, and leukocytes were within normal ranges. Self-reactive antibodies were negative. Histological examination (Figure 1, b) identified rare dyskeratotic keratinocytes and basal lymphocyte infiltrate, a dermal dense fibrosis with the disappearance of the skin appendages, and large fibrous septa in the adipose panniculus. It led to the diagnosis of scleroderma/morphea, based on the patient's clinical history. The diagnosis of graft versus host disease scleroderma-like post liver transplant was established. The lesion was treated by topical application of 0.05% clobetasol once a day. We did not use systemic immunosuppressive therapy in order to prevent HCC recurrence. The pat

Topics: C-Reactive Protein; Clobetasol; Everolimus; Fibrosis; Graft vs Host Disease; Humans; Inflammation; Liver Transplantation; Magnetic Resonance Imaging; Male; Middle Aged; Scleroderma, Localized; Sclerosis; Skin Diseases; Tacrolimus; Ulcer

A 46-year-old man with myelodysplastic syndrome/myeloproliferative neoplasm-unclassifiable underwent myeloablative bone marrow transplantation from an HLA-DR-1-antigen-mismatched related donor while receiving tacrolimus and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. However, grade III acute GVHD of the gut occurred on day 20 and was treated with prednisolone (PSL) and oral beclomethasone dipropionate while continuing MMF. Subsequently, he presented with progressive epigastric pain. Endoscopy demonstrated multiple stomach and duodenal deep ulcers. The ulcers were suspected to be GVHD; thus, the PSL dose was increased and infliximab was administered; however, the ulcers exacerbated, resulting in repeated perforations and hemorrhagic shock. Furthemore, MMF was suspected as the cause of refractory ulcers and was discontinued on day 156, which resolved the ulcers after 6 months. MMF-induced gastrointestinal (GI) injury resembles anti-inflammatory drug-related ulcers and upper and lower GI tract GVHD, respectively. MMF-induced GI injury has been reportedly resolved after discontinuing or reducing the MMF dose. Several reports suggested that refractory upper GI ulcers and rectal sparing colitis were associated with MMF toxicities rather than GVHD in hematopoietic stem cell transplantations. Physicians should be aware that MMF can induce severe GI injury.

Topics: Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Tacrolimus; Ulcer

Post-transplant lymphoproliferative disorder (PTLD) is a well-recognized and potentially fatal complication of cardiac transplantation that commonly involves the gastrointestinal tract. Herein, we report a case of life-threatening gastrointestinal bleeding from recurrent terminal ileac ulcers mimicking PTLD in a heart recipient treated with everolimus (EVL). A 40-year-old man underwent heart transplantation for dilated cardiomyopathy 3 years prior to the current admission and was treated with tacrolimus and EVL. He was admitted to a local hospital because of fever, abdominal pain, and diarrhea. His symptoms persisted and, 3 weeks later, hematochezia occurred; thus, he was transferred to our hospital. As computed tomography and

Topics: Adult; Diagnosis, Differential; Everolimus; Graft Rejection; Heart Transplantation; Humans; Ileal Diseases; Immunosuppressive Agents; Lymphoproliferative Disorders; Male; Mycophenolic Acid; Tacrolimus; Ulcer

Although gastroduodenal ulcers are common in solid organ transplant patients, there are few reports on multiple giant ulcers in the distal ileum and ileocecal valve caused by immunosuppressants Herein, we report on a liver transplant recipient and a renal transplant recipient with multiple large ulcers in the distal ileum and ileocecal valve who rapidly achieved ulcer healing upon withdrawal of sirolimus or tacrolimus and administration of thalidomide. In case 1, a 56-year-old man with primary hepatocellular carcinoma had received a liver transplantation. Tacrolimus combined with sirolimus and prednisolone was used as the anti-rejection regimen. Colonoscopy was performed because of severe abdominal pain and diarrhea at post-operative month 10. Multiple giant ulcers were found at the ileocecal valve and distal ileum. The ulcers healed rapidly with withdrawal of sirolimus and treatment with thalidomide. There was no recurrence during 2 years of follow-up. In case 2, a 34-year-old man with end-stage kidney disease received kidney transplantation and was put on tacrolimus combined with mycophenolate mofetil and prednisolone as the anti-rejection regimen. Twelve weeks after the operation, the patient presented with hematochezia and severe anemia. Colonoscopy revealed multiple large ulcers in the ileocecal valve and distal ileum, with massive accumulation of fresh blood. The bleeding ceased after treatment with intravenous somatostatin and oral thalidomide. Tacrolimus was withdrawn at the same time. Colonoscopy at week 4 of follow-up revealed remarkable healing of the ulcers, and there was no recurrence of bleeding during 1 year of follow-up. No lymphoma, tuberculosis, or infection of cytomegalovirus, Epstein-Barr virus, or fungus was found in either patient. In post-transplantation cases with ulcers in the distal ileum and ileocecal valve, sirolimus or tacrolimus should be considered a possible risk factor, and withdrawing them or switching to another immunosuppressant might be effective to treat these ulcers.

Topics: Adult; Colonoscopy; Deprescriptions; Gastrointestinal Hemorrhage; Graft Rejection; Humans; Ileal Diseases; Immunosuppressive Agents; Kidney Transplantation; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Prednisolone; Sirolimus; Tacrolimus; Ulcer

Systemic lupus erythematosus (SLE) is frequently accompanied by gastrointestinal symptoms. Although all parts of the gastrointestinal tract may be affected, colonic involvement is quite rare. Colonic ulceration, particularly in the rectum, is associated with a high mortality rate in patients with SLE, despite immunosuppressive therapy. While a standard regimen for treating rectal ulcers as a complication of SLE has not been established, combination therapy with steroids and immunosuppressive agents is necessary because of the associated high mortality rate. In this report, we describe a patient with SLE whose condition was complicated with ulcerative lesions in the rectum and sigmoid colon; the lesions were successfully treated with a combination of corticosteroids and tacrolimus therapy. Tacrolimus could be a useful additional or alternative modality for treating rectal involvement in SLE.

Topics: Adrenal Cortex Hormones; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Male; Middle Aged; Rectal Diseases; Tacrolimus; Treatment Outcome; Ulcer

Churg-Strauss syndrome (CSS), which is characterized by systemic small-vessel vasculitis of unknown etiology, is associated with a history of asthma. Although reports of CSS occurring in children are limited, effective treatment of pediatric patients with severe CSS remains challenging. A 10-year-old Japanese boy with a 6-month history of asthma treated with a leukotriene modifier, pranlukast, developed high fever, pleural infiltration, and pericarditis that were associated with marked hypereosinophilia (10,350 eosinophils/µl). Owing to his persistent high fever, mononeuritis multiplex, and severe abdominal pain that was refractory to prednisolone, his general condition progressively deteriorated thereafter. Although intravenous high-dose immunoglobulin administration was transiently effective for mononeuritis multiplex, the recurrent high fever and severe abdominal pain remained refractory. An endoscopic study revealed ulcerative lesions of the total colon. In this context, we treated the patient with an aggressive multidrug immunosuppressive regimen consisting of a high-dose methylprednisolone pulse plus short-course intravenous cyclophosphamide pulse therapy, followed by oral tacrolimus combined with prednisolone. After the rescue multidrug treatment, his severe clinical signs dramatically subsided within a short time, and the concomitantly administered prednisolone was successfully tapered without flare. At present, 12 months after the presentation, he is free from CSS signs or therapy-related toxicity except for an occasional mild asthma attack. Although further close observation should be needed to draw a long-term outcome in this patient, we believe that aggressive multidrug immunosuppressive treatment should be considered as an alternative rescue treatment in selected patients with severe CSS, even with pediatric-onset disease, that is refractory to prednisolone.

Topics: Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Child; Chromones; Churg-Strauss Syndrome; Cyclophosphamide; Drug Resistance; Drug Resistance, Multiple; Eosinophilia; Humans; Immunosuppressive Agents; Japan; Methylprednisolone; Pericarditis; Pleura; Prednisolone; Tacrolimus; Ulcer

Topics: Administration, Oral; Administration, Topical; Adolescent; Arthritis, Juvenile; Humans; Immunosuppressive Agents; Male; Methotrexate; Prednisolone; Pyoderma Gangrenosum; Tacrolimus; Treatment Outcome; Ulcer

We examined the effect of tacrolimus (FK506), an immunosuppressive drug, on indomethacin-induced small intestinal ulceration in rats. Animals were given indomethacin (10 mg/kg, s.c.), killed 24 h later, and myeloperoxidase (MPO) activity and thiobarbituric acid reactants (TBARS) were evaluated in intestinal lesions. Tacrolimus (0.3 - 3 mg/kg) was administered p.o. twice 0.5 h before and 6 h after indomethacin injection. The expression of inducible nitric oxide synthase (iNOS) mRNA was determined by a TaqMan real-time RT-PCR, while the activity of nuclear factor (NF)-kappaB DNA-binding was analyzed by electrophoresis mobility shift assays (EMSA) 6 h after indomethacin treatment. Indomethacin provoked severe hemorrhagic lesions in the small intestine, mainly in the jejunum and ileum, accompanied with increases in MPO activity and TBARS. Oral administration of tacrolimus reduced the severity of indomethacin-induced intestinal lesions in a dose-dependent manner. The increases in MPO activity and TBARS were also significantly attenuated by tacrolimus. The expression of iNOS mRNA was markedly enhanced when examined 6 h after indomethacin administration, and this response was counteracted by tacrolimus. Indomethacin also activated NF-kappaB in a tacrolimus-preventable manner. These results suggest that tacrolimus prevents indomethacin-induced small intestinal ulceration in the rat. This effect may be due to inhibition of iNOS induction through suppression of NF-kappaB activation.

Topics: Animals; Immunosuppressive Agents; Indomethacin; Intestinal Diseases; Lipid Peroxidation; Male; NF-kappa B; Nitric Oxide Synthase Type II; Peroxidase; Rats; Rats, Sprague-Dawley; RNA, Messenger; Tacrolimus; Tumor Necrosis Factor-alpha; Ulcer

Infection due to cytomegalovirus (CMV) is the most frequent opportunistic infection following renal transplantation (RT). It is usually asymptomatic. Cytomegalovirus disease causes fever leucopenia, thrombocytopenia and slightly elevated transaminases. The development of severe invasive forms is uncommon nowadays with post-transplantation monitoring, prophylactic regimens in high-risk patients and early treatment with ganciclovir. We report two renal transplant recipients who presented with severe gastrointestinal bleeding as the first manifestation of CMV disease at 9 and 14 weeks after transplantation. In both patients repeated post-transplantation pp65 antigenemia monitoring was negative. One patient developed hypovolemic shock due to severe rectal bleeding; an atypical bleeding ulcer was detected in the ileocecal valve. The other patient presented with upper gastrointestinal hemorrhage from a bleeding duodenal ulcer. Histological and immunohistochemical study confirmed the diagnosis. Both patients were elderly and on triple therapy with tacrolimus, mycophenolate and prednisone. We discuss the role of mycophenolate and the new immunosuppressant agents as factors favoring a state of enhanced immunosuppression, which may facilitate the onset of severe atypical forms of CMV disease.

Topics: Aged; Cytomegalovirus; Cytomegalovirus Infections; Disease Susceptibility; Duodenal Ulcer; Gastrointestinal Hemorrhage; Humans; Ileal Diseases; Ileocecal Valve; Immunocompromised Host; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Opportunistic Infections; Postoperative Complications; Prednisone; Shock; Tacrolimus; Ulcer