tacrolimus and Sjogren-s-Syndrome

A 69-year-old woman, who had been diagnosed as having Sjögren's syndrome at 37 years old and mixed connective tissue disease at 42 years old, was under treatment with oral prednisolone. In 2009, she was diagnosed as having active systemic lupus erythematosus, and started on treatment with tacrolimus at 3 mg/day. In 2010, para-aortic lymphadenopathy and superficial multiple lymphadenopathy were detected. Tacrolimus was discontinued. Axillary lymph node biopsy revealed Epstein-Barr (EB) virus-negative CD5-positive diffuse large B-cell lymphoma (DLBCL). The patient was classified into clinical stage IIIA and as being at high risk according to the international prognostic index. After the discontinuation of tacrolimus, the lymph nodes reduced temporarily in size. In January 2011, the lymphadenopathy increased again, and the patient received a total of 8 courses of therapy with rituximab, pirarubicin, vincristine, cyclophosphamide and prednisolone, followed by intrathecal injection to prevent central nervous system infiltration, which was followed by complete remission. In February 2012, fluorodeoxyglucose positron emission tomography showed relapse in multiple lymph nodes and central nervous system infiltration. The patient was considered to have iatrogenic lymphoproliferative disorder classified as "other iatrogenic immunodeficiency-associated lymphoproliferative disorders" by the WHO, and this is the first reported case of CD5-positive DLBCL and central nervous system infiltration following administration of the drug. The patient was considered to have a poor prognosis as EB virus was negative, discontinuation of tacrolimus was ineffective and there was evidence of central nervous system infiltration.

Topics: Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; CD5 Antigens; Cyclophosphamide; Doxorubicin; Female; Herpesvirus 4, Human; Humans; Iatrogenic Disease; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lymphoma, Large B-Cell, Diffuse; Mixed Connective Tissue Disease; Prednisolone; Rituximab; Sjogren's Syndrome; Tacrolimus; Vincristine

Annular erythema has been recognized to be a specific, cutaneous manifestation associated with Sjögren's syndrome. Based on a search of the literature up to 2007, annular erythema with Sjögren's syndrome (AESS) preferentially occurs in Asian but not in Western populations. However, the precise clinical course and standard regimen for the management of AESS have remained obscure, primarily because of its rare occurrence in Western populations and the fact that most Asian cases are isolated reports. In this study, 28 cases of AESS from our department and 92 cases distilled from the literature were enrolled in a retrospective study to evaluate the clinical characteristics and most desirable management of this skin manifestation in Sjögren's syndrome. We found that 75% of all cases with AESS were positive for both anti-SSA and anti-SSB antibodies. Multiple therapeutic options are available to treat AESS, including oral steroids. Several anti-malaria drugs or tacrolimus ointment have also been reported to be effective against AESS. AESS is a distinct clinical entity, and a small dose of prednisolone (approx. 10 mg) is sufficient to control diseases activity, except in some cases with systemic manifestations, and this treatment has a more rapid clinical effect than topical steroids.

Topics: Administration, Oral; Administration, Topical; Anti-Inflammatory Agents; Antimalarials; Asian People; Dose-Response Relationship, Drug; Erythema; Humans; Prednisolone; Sjogren's Syndrome; Tacrolimus

To compare the effect of topical application of tacrolimus 0.03% eyedrops versus cyclosporine 0.05% in Sjogren syndrome subjects with severe dry eyes.. A prospective single-blinded simply randomized controlled study.. 60 Sjogren patients were randomized intoGroup A: 30 patients were instructed to put tacrolimus 0.03% eyedrops in one eye for 6 months and placebo eyedrops in the other eye, (. Upon comparing both eyedrops, the mean value of OSDI decrease was 38.25 ± 18.29% versus 31.69 ± 18.57% (. Both tacrolimus and cyclosporine significantly improved patient symptoms, frequency of artificial tears use and ocular surface staining compared to placebo-controlled eyes. However, no significant difference regarding the efficacy of both eyedrops at the end of 6 months treatment of severe dry eyes of Sjögren syndrome patients.. ClinicalTrials.gov. Identifier: NCT03865888.

Topics: Cyclosporine; Dry Eye Syndromes; Humans; Lubricant Eye Drops; Ophthalmic Solutions; Prospective Studies; Sjogren's Syndrome; Tacrolimus; Tears

To describe the clinical efficacy of the treatment of Sjögren's syndrome dry eye using 0.03% tacrolimus eye drop.. Prospective double-blind randomized study.. Institutional outpatient clinic.. Forty-eight eyes of twenty-four patients with dry eye related to Sjögren syndrome were enrolled in this study. The patients were randomized in 2 groups: tacrolimus (n=14) and vehicle (n=10) group.. The tacrolimus group received a vial containing tacrolimus 0.03% (almond oil as vehicle) and the other group received the almond oil vehicle. All patients were instructed to use the eye drops every 12h in the lower conjunctival sac.. Schirmer I test, break-up-time (BUT), corneal fluorescein and Rose Bengal staining scores were evaluated in all patients one day before the treatment (baseline), 7, 14, 28 and 90 days after treatment with the eye drops.. The average fluorescein and Rose Bengal scores improved statistically after 7 days of treatment and even more after 90 days. The average Schirmer I and BUT values were unchanged after 7, 14 and 21 days but did show an improvement relative to baseline after 28 days of treatment. Schirmer I, BUT, fluorescein and Rose Bengal did not show any statistical significance in the vehicle group.. Topical 0.03% tacrolimus eye drop improved tear stability and ocular surface status in cases of inflammatory or SS-related dry eye.. ClinicalTrials.gov Identifier: NCT01850979.

Topics: Administration, Ophthalmic; Double-Blind Method; Dry Eye Syndromes; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Ophthalmic Solutions; Prospective Studies; Sjogren's Syndrome; Tacrolimus; Tears; Treatment Outcome

Topics: Dry Eye Syndromes; Hair Diseases; Humans; Patients; Sjogren's Syndrome; Tacrolimus

To evaluate the efficacy and safety of tacrolimus (TAC) for the treatment of primary Sjögren's syndrome (pSS) with refractory immune thrombocytopenia (RITP).. Twenty-three pSS patients with RITP treated with TAC from June 2018 to June 2021 at the First Affiliated Hospital of Soochow University were enrolled in this retrospective cohort study. Platelet response, clinical and immunological parameters, toxicity and safety were compared and analysed at baseline and different points after TAC treatment.. At 4 weeks after treatment, 2 patients (8.7%) attained a complete response (CR, platelet count ≥100×109/L and no bleeding), 15 patients (65.2%) achieved a partial response (PR, platelet count ≥ 30×109/L but <100×109/L and no bleeding or a platelet count at least twice that before treatment), and the other 6 patients (26.1%) did not respond to TAC treatment. At 8 weeks after treatment, a CR was seen in 4 patients (17.4%), and the percentage of patients with a PR increased to 78.3% (18 patients). The percentage of patients with a CR increased to 47.8% (11 patients), and 9 patients (39.1%) achieved a PR without relapse at 12 weeks after treatment. At 24 weeks after treatment, 14 patients (60.9%) achieved a CR, and 8 patients (34.8%) achieved a PR. Compared to before treatment, the level of IgG was decreased significantly at 24 weeks after treatment, whereas there was no significant difference in the levels of IgM or IgA between baseline and 24 weeks after treatment. Additionally, the absolute CD3+ T cell count, European SS Disease Activity Index (ESSDAI) score, and levels of IL-2 and INF-γ were significantly decreased at 24 weeks after treatment.. TAC is effective and well tolerated by pSS patients with RITP, and the mechanism underlying the effect of TAC in these patients may be related to reduced Th1 cytokine expression.

Topics: Humans; Platelet Count; Purpura, Thrombocytopenic, Idiopathic; Retrospective Studies; Sjogren's Syndrome; Tacrolimus

We herein report an unusual case of primary Sjögren's syndrome in a 38-year-old woman with typical clinical symptoms (joint pain, dry mouth, and positive Schirmer test) and immunoglobulin G positivity but negativity for antinuclear antibody and all antinuclear antibody spectrum antibodies. Emission computed tomography demonstrated normal ingestion but impaired secretion by the submandibular and bilateral parotid glands. Labial gland biopsy revealed chronic tissue inflammatory changes and Chisholm grade 4 lymphocyte infiltration, confirming primary Sjögren's syndrome. The patient's condition was successfully controlled by nonsteroidal treatment with tacrolimus. Patients presenting with chronic dry mouth should be examined by a Schirmer test, lip gland biopsy, and salivary gland emission computed tomography for possible Sjögren's syndrome, even if serological autoantibodies are negative, to facilitate early intervention. Tacrolimus is a potential treatment option in patients intolerant of steroidal drugs.

Topics: Adult; Antibodies, Antinuclear; Female; Humans; Salivary Glands; Sjogren's Syndrome; Tacrolimus; Tomography, X-Ray Computed

Interstitial lung disease (ILD) is a significant complication of Sjögren syndrome (SS) associated with increased morbidity and mortality. The mainstay of treatment remains corticosteroid administration, with or without additional immunosuppressive therapies. Preliminary studies in SS have shown benefit in glandular and serologic parameters following treatment with the CTLA4 immunoglobulin fusion protein abatacept. Topical tacrolimus has been effective for ocular symptoms in SS, but systemic therapy has not been reported. We describe the first case, to our knowledge, of the successful use of a combination of systemic tacrolimus and abatacept in severe refractory SS and related ILD.

Topics: Abatacept; Female; Humans; Immunosuppressive Agents; Lung Diseases, Interstitial; Middle Aged; Respiratory Function Tests; Rituximab; Sjogren's Syndrome; Tacrolimus

A 33 year-old woman presented with intentional incontinence, motor aphasia, supranuclear gaze palsy, and spasticity after parotitis. Brain magnetic resonance images (MRI) showed abnormal signaling in long corticospinal tract involving internal capsules and cerebral peduncles, middle cerebellar peduncle, and frontal subcortical white matter lesions. She had a long history of dry eye and mouth. Immunoserological study showed that she was positive for anti-SS-A, aquaporin 4 (AQP4), and AQP5 antibodies. She clinically showed not only Sjögren's syndrome but also neuromyelitis optica spectrum disorder (NMOSD) without optic neuritis or myelitis. She responded to steroid followed by plasma exchange dramatically. Thereafter, the relapse of brain lesion was once detected while tapering of steroid, but her symptoms have been stable for several years after administration of immunosuppressant. This case suggested that salivary gland inflammation might be associated with the pathogenesis of NMOSD.

Topics: Adult; Autoantibodies; Biomarkers; Brain; Female; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Methylprednisolone; Neuromyelitis Optica; Parotitis; Plasma Exchange; Pulse Therapy, Drug; Recurrence; Sjogren's Syndrome; Tacrolimus; Treatment Outcome

We report a case of interstitial cystitis (IC) associated with primary Sjögren's syndrome (SS) successfully controlled with combination therapy of tacrolimus and a corticosteroid. In 2011, a 69-year-old female, who had been diagnosed with primary SS 23 years ago, developed IC and was successfully treated with tacrolimus and prednisolone combination therapy. The mechanism of IC, including the involved autoimmunity, has not been elucidated. Clinical observation studies suggest a potential association between SS and IC. However, IC is currently thought to be underdiagnosed in patients with SS as well as in the general population. Based on our case and others reported previously, IC associated with SS responds well to immunosuppressive therapy. In particular, a combination of a calcineurin inhibitor (tacrolimus or cyclosporine) with a corticosteroid seems to be highly effective. The possibility of IC in patients with SS complaining of lower urinary tract symptoms without features of infection or other identifiable causes should be given attention.

Topics: Adrenal Cortex Hormones; Aged; Cystitis, Interstitial; Drug Therapy, Combination; Female; Humans; Prednisolone; Sjogren's Syndrome; Tacrolimus; Treatment Outcome

Tacrolimus, a novel immunosuppressant agent, has been widely used in organ transplantation and autoimmune diseases. We herein present a case of neuromyelitis optica spectrum disorder (NMOSD) combined with Sjögren's syndrome (SS) successfully treated with tacrolimus. This patient repeatedly presented with recurrent longitudinally extensive transverse myelitis. Her NMO-IgG and anti-SSA and anti-SSB antibodies were seropositive. Considering the frequency of relapses and severe disability, tacrolimus was initiated after failure of intravenous cyclophosphamide. Her status was steady for over 36 months after tacrolimus treatment. This report indicates that tacrolimus may be a potentially effective immunosuppressant for NMOSD with systemic autoimmune diseases.

Topics: Adult; Autoantibodies; Cyclophosphamide; Female; Humans; Immunoglobulin G; Immunosuppressive Agents; Neoplasm Recurrence, Local; Neuromyelitis Optica; Sjogren's Syndrome; Tacrolimus

To report the clinical outcome of the treatment of dry eyes using 0.03% tacrolimus eye drops (olive oil + tacrolimus 0.03%) (Ophthalmos, Sao Paulo, Brazil).. Sixteen eyes of 8 patients with Sjögren syndrome dry eyes (age, 51.13 ± 9.45 years) were enrolled in this study (prospective noncontrolled interventional case series). Patients were instructed to use topical 0.03% tacrolimus eye drops twice a day (every 12 hours) in the lower conjunctival sac. Schirmer I test, break-up time, corneal fluorescein, and rose bengal staining score were performed in all patients 1 day before, and 14, 28, and 90 days after treatment with 0.03% tacrolimus eye drops.. The average fluorescein staining and rose bengal staining scores improved statistically significantly after 14 days of treatment and improved even more after 28 and 90 days. The average Schirmer I test did not improve statistically significantly after 28 days of treatment, although we did observe a significant improvement after 90 days of treatment with 0.03% tacrolimus eye drops. The average break-up time did not improve statistically after 14 days of treatment, although we observed a significant improvement after 28 and 90 days of treatment with 0.03% tacrolimus eye drops.. Topical 0.03% tacrolimus eye drops successfully improved tear stability and ocular surface status in patients with dry eyes.

Topics: Administration, Topical; Fluorescent Dyes; Fluorophotometry; Humans; Immunosuppressive Agents; Middle Aged; Ophthalmic Solutions; Prospective Studies; Rose Bengal; Sjogren's Syndrome; Tacrolimus; Tears; Treatment Outcome

A 56-year-old HTLV-I-positive woman, initially diagnosed as having Sjögren's syndrome, presented with muscle weakness, myalgia, face erythema and leg edema. Based on the presence of various autoantibodies, the diagnosis of overlap syndrome (dermatomyositis/Sjögren's syndrome) was made. Treatment with high-dose corticosteroid plus cyclosporine improved her symptoms. However, three months after the start of these treatments, exacerbation of myositis occurred. A muscle biopsy revealed prominent perivascular accumulation of mononuclear cells with perifascicular atrophy, which were consistent with dermatomyositis. Tacrolimus, which was substituted for cyclosporine led to marked improvement of the myositis symptoms.

Topics: Dermatomyositis; Female; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Middle Aged; Sjogren's Syndrome; Tacrolimus; Treatment Outcome

Topics: Aquaporin 4; Autoantibodies; Brain; Central Nervous System Diseases; Female; Humans; Immunosuppressive Agents; Middle Aged; Sjogren's Syndrome; Spinal Cord; Tacrolimus; Treatment Outcome

Serial changes in the circulating and cerebrospinal fluid (CSF) cytokine levels were assessed in a patient with Sjogren's syndrome (SS)-associated meningoencephalomyelitis. A 16-yr-old girl diagnosed as having primary SS at 8 yr of age presented headache and vomiting. CSF studies revealed lymphocyte-dominant pleocytosis and high IgM index, but no evidence of infection. Disturbed consciousness and diffuse slow waves on electroencephalogram led to the diagnosis of SS-meningoencephalitis. The clinical condition subsided after a cycle of dexamethasone therapy, however, 2 months later urinary retention and paresthesia of the lower body developed. Craniospinal magnetic resonance imaging (MRI) showed extensive intraparenchymal lesions with high T2-weighted signal intensity adjacent to the posterior left horn of lateral ventricle of the brain and the longitudinal lesion from C5 to T10 of the spinal cord. High-dose methyl-prednisolone and subsequent tacrolimus therapy has effectively controlled the activity of SS-meningoencephalomyelitis. Monitoring of systemic and CSF cytokine levels during the course of illness revealed that CSF interleukin-6, but not interferon-gamma or tumor necrosis factor-alpha levels were the sensitive indicator of disease activity. The unique cytokine profile, differing from those of infectious meningitis may be useful for predicting the central nervous system involvement in autoimmune disease.

Topics: Adolescent; Anti-Inflammatory Agents; Biomarkers; Brain; Cytokines; Dose-Response Relationship, Drug; Female; Headache; Humans; Immunosuppressive Agents; Interleukin-6; Magnetic Resonance Imaging; Meningoencephalitis; Methylprednisolone; Monitoring, Physiologic; Myelitis; Predictive Value of Tests; Sjogren's Syndrome; Spinal Cord; Tacrolimus; Treatment Outcome; Vomiting

Topics: Adult; Erythema; Facial Dermatoses; Female; Humans; Immunosuppressive Agents; Sjogren's Syndrome; Tacrolimus

The influence of the Ipr(cg) gene on the development of Sjögren's syndrome was followed up to 5 months of age in male and female mice of MRL, CBA and C3H strains. In MRL-Ipr(cg) mice, focal mononuclear cell infiltration started at 2 months and became conspicuous after 3 months of age in the lacrimal and submandibular glands but was minimal in the parotid and sublingual glands, even at 5 months of age, without any apparent sex effects found. In CBA and C3H mice carrying the Ipr(cg) gene, this manifestation of Sjögren's syndrome was much less prominent, indicating that the participation of some genes of the MRL strain may be indispensable for the development of Sjögren's syndrome in mice carrying this gene. In MRL-Ipr(cg) mice, an immunosuppressive agent, FK506, improved the serological abnormalities (decreased levels of anti-double-stranded DNA antibody of IgG2a and IgG3 subclasses) and proteinuria. It also reduced the manifestations of Sjögren's syndrome when it was intraperitoneally administered three times weekly at a dose of 2 mg/kg from 6 weeks (before disease onset) until 5 months of age (the termination of the experiment). Although VP8.2+ T cells have been demonstrated to be responsible for causing several autoimmune diseases, the selective deletion of Vp8.2+ T cells with the superantigen encoded by mouse mammary tumor virus did not affect the disease severity at all, suggesting that this T cell repertoire may not play a crucial role in induction of Sjögren's syndrome.

Topics: Animals; Antibodies, Antinuclear; DNA; Enzyme-Linked Immunosorbent Assay; fas Receptor; Female; Flow Cytometry; Immunoglobulin G; Immunosuppressive Agents; Lacrimal Apparatus; Male; Mice; Mice, Inbred C3H; Mice, Inbred CBA; Mice, Inbred MRL lpr; Proteinuria; Sjogren's Syndrome; Submandibular Gland; Tacrolimus