mycophenolic-acid and Sjogren-s-Syndrome

Lung involvement in rheumatologic diseases has a broad spectrum of clinical and radiological presentations, from acute and inflammatory predominance to chronic and fibrotic lung disorders. Therapy has to be guided by the type of rheumatologic disease, the kind of lung involvement and the risk associated with the clinical state of the patient and prognostic factors. Although several therapeutic approaches have been used, the best treatment is still not certain; clinical trials are mandatory, which would require a better knowledge of the pulmonary pathogenesis of immunologic diseases. The following review is focused on the therapeutic options for those rheumatologic disorders that could present as a predominant interstitial lung disease which may confer a bad or life-threatening prognosis.

Topics: Adrenal Cortex Hormones; Antirheumatic Agents; Arthritis, Rheumatoid; Azathioprine; Cyclophosphamide; Humans; Immunosuppressive Agents; Lung Diseases; Lupus Erythematosus, Systemic; Mycophenolic Acid; Polymyositis; Rituximab; Scleroderma, Systemic; Sjogren's Syndrome

Topics: Abatacept; Antibodies, Monoclonal, Murine-Derived; Azathioprine; Combined Modality Therapy; Glomerulonephritis, IGA; Glucocorticoids; Humans; Immunoconjugates; Kidney Glomerulus; Lupus Nephritis; Mycophenolic Acid; Nephrosis, Lipoid; Nephrotic Syndrome; Prognosis; Rituximab; Sjogren's Syndrome; Tonsillectomy

The aim of this study was to evaluate the efficacy and safety of mycophenolate sodium (MPS) in patients with primary Sjögren syndrome (pSS) refractory to other immunosuppressive agents. Eleven patients with pSS were treated with MPS up to 1,440 mg daily for an observation period of 6 months in this single-center, open-label pilot trial. At baseline, after 3 months, and after 6 months, we examined the clinical status, including glandular function tests, as well as different laboratory parameters associated with pSS. In addition, subjective parameters were determined on the basis of different questionnaires. Treatment with MPS was well tolerated in 8 of 11 patients. Due to vertigo or gastrointestinal discomfort, two patients did not complete the trial. One patient developed pneumonia 2 weeks after treatment and was withdrawn. In the remaining patients, MPS treatment resulted in subjective improvement of ocular dryness on a visual analogue scale and a reduced demand for artificial tear supplementations. However, no significant alterations of objective parameters for dryness of eyes and mouth were observed, although a substantial improvement of glandular functions occurred in two patients with short disease duration. In addition, treatment with MPS resulted in significant reduction of hypergammaglobulinemia and rheumatoid factors as well as an increase of complement levels and white blood cells. MPS promises to be an additional therapeutic option for patients with pSS, at least in those with shorter disease duration. Further investigations about the efficacy and safety of MPS in pSS have to be performed in larger numbers of patients.

Topics: Adult; Aged; Drug Tolerance; Female; gamma-Globulins; Humans; Immunosuppressive Agents; Lacrimal Apparatus; Middle Aged; Mycophenolic Acid; Prospective Studies; Safety; Saliva; Sjogren's Syndrome; Surveys and Questionnaires; Xerophthalmia

Topics: Adolescent; Antibiotics, Antitubercular; Female; Humans; Immunosuppressive Agents; Mycophenolic Acid; Neuromyelitis Optica; Sjogren's Syndrome; Treatment Outcome

Topics: Aged; Antirheumatic Agents; Biopsy; Diagnosis, Differential; Female; Glucocorticoids; Humans; Immunoglobulins; Mycophenolic Acid; Neurologic Examination; Peripheral Nervous System Diseases; Remission Induction; Salivary Glands; Sjogren's Syndrome; Treatment Outcome; Xerophthalmia; Xerostomia

A 29-year-old woman who is a never smoker and has a medical history of systemic hypertension presented with a 3-week history of generalized fatigue and dry cough. She endorsed sicca symptoms of dry eyes and dry mouth. She denied breathlessness, fever, chills, night sweats, or weight loss. She had no heartburn, postnasal drip, joint pain, swelling, or skin lesions. She had no known lung disease or history of pneumothorax. Her family history was unremarkable.

Topics: Adult; Cough; Cysts; Diagnosis, Differential; Enzyme Inhibitors; Female; Humans; Immunoglobulin Light Chains; Lung Diseases; Multiple Pulmonary Nodules; Mycophenolic Acid; Sjogren's Syndrome

Interstitial lung disease (ILD) is a common complication of primary Sjögren's syndrome (pSS). Because there is a paucity of literature on the management of pSS-associated ILD (pSS-ILD), this retrospective cohort study assessed the efficacy of azathioprine and mycophenolate therapy in adult patients with pSS-ILD.. A retrospective cohort study was performed using electronic health records to identify adults meeting the 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for pSS. The presence of pSS-ILD was confirmed by characteristic high-resolution computed tomography and/or histopathology findings. Sociodemographic, clinical, and pulmonary function test (PFT) data were abstracted for patients meeting the criteria and followed longitudinally from the date of their ILD diagnosis. PFT values were anchored on time of treatment start, and linear mixed-effects modeling was used to analyze changes in diffusion capacity for carbon monoxide (DLCO) and forced vital capacity (FVC) before and after treatment initiation.. We identified 19 subjects who had pSS-ILD, of whom seven were treated with azathioprine and seven were treated with mycophenolate. Within the azathioprine treated group, FVC% slope change trended toward improvement from a rate of -9.8% per month pre-treatment to 2.1% per month post-treatment (p = 0.13). Within the mycophenolate treated group, FVC% slope change improved from a rate of 1.5% per month pre-treatment to 4.3% per month post-treatment (p = 0.02) and DLCO% slope changed from a rate of -3.8% to -1.3% per month (p = 0.01) after therapy start.. Mycophenolate treatment was associated with significant improvement in PFTs of pSS-ILD patients over time, and azathioprine treatment followed a similar non-significanttrend. Additional prospective studies are needed to further evaluate these findings.

Topics: Aged; Aged, 80 and over; Azathioprine; Electronic Health Records; Female; Humans; Immunosuppressive Agents; Lung; Lung Diseases, Interstitial; Male; Middle Aged; Mycophenolic Acid; Recovery of Function; Retrospective Studies; Sjogren's Syndrome; Time Factors; Treatment Outcome

The aim of this study is to describe the clinical features of cerebellar involvement in patients with primary Sjögren's syndrome (pSS). We retrospectively analyzed the manifestations, treatments, and outcomes in patients with pSS-cerebellar complication in Peking Union Medical College Hospital and cases reported in literature. Altogether 13 patients were identified. They were 2 males and 11 females with a mean age at disease onset of 45.2 ± 14.6 years. Nine (69.2%) patients went to the clinic because of ataxia, and pSS was not suspected until accidental screening for autoantibodies. Dysarthria (7, 59.8%), limb tremor (4, 30.8%), and nystagmus (2, 15.4%) were the rest symptoms related to cerebellum. Of the patients, 81.8% (9/11) had abnormal cerebrospinal fluid findings, and 11 patients (84.6%) had cerebellar atrophy in the brain MRI. Dry eyes and dry mouth were detected in 9 (69.2%) and 7 (59.8%) patients, while positive objective xerostomia and ocular test in 82.5% (7/8) and 100% (10/10) of the patients, respectively. Anti-Ro/SSA antibody was positive in 12 (92.3%) and anti-La/SSB in 6 (46.2%) patients. Glucocorticoids were applied in 12 patients (92.3%). Cyclophosphamide (3, 20.1%), mycophenolatemofetil (1, 7.7%), and hydroxychloroquine (4, 30.8%) were chosen as immunosuppressants or anti-inflammatory drug. During a median follow-up of 9 months (range, 1-18 months), 8 (61.5%) patients remained stable, 3 (20.1%) patients were in remission, and 2 (15.4%) patients were in progression. Clinical cerebellar complication secondary to pSS was rare, and sometimes pSS was not suspected until accidental screening for autoantibodies. Because the onset of cerebellar manifestation is often insidious and rapid deteriorates, early diagnosis and empirical aggressive glucocorticoid treatment is warranted.

Topics: Adult; Cerebellar Diseases; Cyclophosphamide; Female; Glucocorticoids; Humans; Male; Middle Aged; Mycophenolic Acid; Retrospective Studies; Sjogren's Syndrome; Young Adult

BACKGROUND Sjögren's syndrome is a chronic inflammatory autoimmune disease, which is also known as sicca syndrome, due to the symptoms of dry eyes and dry mouth, and is associated with other connective tissue diseases and autoimmune diseases. Sjögren's syndrome can also be associated with renal involvement. Fanconi's syndrome is associated with impaired reabsorption in the proximal renal tubule associated with tubulointerstitial nephritis and is associated with renal tubular acidosis and hypophosphatemia. Osteomalacia is a rare association with Sjögren's syndrome, which may result from renal disease. CASE REPORT We report the case of a 34-year-old woman who presented with xerostomia, xerophthalmia, bone fractures, and osteomuscular pain. A Schirmer test showed reduced tear production, and a biopsy of a minor salivary gland of the lip, with high titers of antinuclear antibodies (ANA), and positive anti-SSA/Ro and anti-SSB/La antibodies confirmed the diagnosis of Sjögren's syndrome. Serum and urinary laboratories tests and clinical manifestations confirmed Fanconi's syndrome associated with osteomalacia. The patient was treated with potassium supplements, 25-hydroxyvitamin D (25(OH)D), hydroxychloroquine, mycophenolate mofetil, and prednisone, with a favorable response. CONCLUSIONS This case is of a rare association between Sjögren's syndrome, Fanconi's syndrome, and osteomalacia. Even though these are rare clinical associations, early detection can improve the quality of life and prevent further complications.

Topics: Adult; Antibiotics, Antineoplastic; Antirheumatic Agents; Biopsy; Drug Therapy, Combination; Fanconi Syndrome; Female; Glucocorticoids; Humans; Hydroxychloroquine; Magnetic Resonance Imaging; Mycophenolic Acid; Osteomalacia; Potassium; Prednisone; Sjogren's Syndrome; Tomography, X-Ray Computed; Vitamin D

Autoimmune diseases are sometimes associated with immune-mediated renal diseases and cryoglobulinemia is one of the causes. Cryoglobulinemia and cryoglobulinemic glomerulonephritis associated with primary Sjögren's syndrome are most frequent condition among non-hepatitis C virus-related condition. Its typical renal manifestation shows high amount of proteinuria with microscopic hematuria and renal insufficiency. We describe a case of 72-year-old woman with Hashimoto disease, autoimmune hepatitis, Sjögren's syndrome, and immune-related pancytopenia complicated by cryoglobulinemic glomerulonephritis. Before kidney biopsy, tubulointerstitial nephritis probably due to Sjögren's syndrome was suspected because of persistent hematuria without significant proteinuria and developing mild renal dysfunction over 6 months. The developing renal dysfunction associated with isolated hematuria is uncommon in glomerular diseases. Kidney biopsy, however, revealed established membranoproliferative glomerulonephritis with subendothelial deposits consisting of tubular structures with IgM, IgG, and C3 staining. Corticosteroids plus mycophenolate mofetil therapy successfully normalized renal function. Physician should not overlook cryoglobulinemic glomerulonephritis, which is potentially poor prognosis, even if urinalysis shows only persistent isolated hematuria in patients with autoimmune diseases.

Topics: Adrenal Cortex Hormones; Aged; Antibiotics, Antineoplastic; Autoimmune Diseases; Cryoglobulinemia; Female; Glomerulonephritis; Glomerulonephritis, Membranoproliferative; Hashimoto Disease; Hematuria; Hepatitis, Autoimmune; Humans; Kidney; Methylprednisolone; Mycophenolic Acid; Nephritis, Interstitial; Pancytopenia; Renal Insufficiency; Sjogren's Syndrome; Treatment Outcome

Topics: Adult; Antibiotics, Antineoplastic; Biopsy; Female; Humans; Kidney; Kidney Function Tests; Mycophenolic Acid; Nephritis, Interstitial; Sjogren's Syndrome; Treatment Outcome

Primary Sjögren syndrome (pSS) is a common autoimmune condition which primarily affects epithelial tissue, often including the kidney causing either tubulointerstitial nephritis (TIN) or more rarely, an immune complex related glomerulonephritis.. We describe the clinical, biochemical and histological characteristics of 12 patients with pSS related TIN and their response to treatment with antiproliferative agents. All 12 patients were investigated and treated at the UCL Centre for Nephrology in London.. All patients had TIN demonstrated via needle biopsy; immunophenotyping showed that the interstitial infiltrate was predominantly a CD4+ T-cell infiltrate. Urinary acidification testing demonstrated distal renal tubular acidosis in 8 patients. Proximal tubular dysfunction was present in 5 patients. All but 1 patient were treated with antiproliferative agents and most also with a reducing course of steroids. In the treated patients, there was a significant improvement in the serum creatinine and measured GFR.. Patients with pSS TIN have significant renal impairment and other functional tubular defects. There is a mononuclear lymphocytic infiltrate on renal biopsy and this appears to be mainly a CD4+ T-cell infiltrate. Treatment with mycophenolate (and corticosteroids) improves the renal function in patients with pSS TIN.

Topics: Adrenal Cortex Hormones; Adult; Aged; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Nephritis, Interstitial; Sjogren's Syndrome; Treatment Outcome

Although most commonly encountered in patients with human immunodeficiency virus infection, disseminated Mycobacterium avium complex (MAC) is becoming more common in patients receiving immunosuppressive medications. Disseminated MAC with skin lesions may occur, and several presentations have been reported, including panniculitis, cutaneous granulomas, pustules, ulcerations, and erythematous skin lesions.. The objective of this report is to describe an unusual presentation of MAC that is unlikely to be encountered frequently in the outpatient dermatology setting, especially in a patient without human immunodeficiency virus infection.. The authors present a case of disseminated MAC infection with cutaneous manifestations in an iatrogenically immunocompromised patient.. Diagnosis of MAC infection is challenging given the varied clinical presentations and the difficulty in culturing MAC. In addition, the acid-fast stain is nonspecific. Clinicians should remember to consider MAC infection in patients with acid-fast-positive skin lesions, as the selection of appropriate antibiotic therapy is species specific.

Topics: Aged; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Lung Diseases; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycophenolic Acid; Sjogren's Syndrome; Skin Diseases, Bacterial; Spondylarthropathies

Hypophysitis is an inflammatory disorder of the pituitary gland and corticosteroids are usually recommended as the first-line treatment. Hypophysitis related to primary Sjögren syndrome (pSS) is uncommon. We describe the unusual case of a patient with infundibuloneurohypophysitis associated with pSS successfully treated with mycophenolate mofetil (MMF).We describe a case of a 60-year-old man with a medical history of pSS presented with central diabetes insipidus and panhypopituitarism. Magnetic resonance imaging (MRI) revealed a thickening of the pituitary stalk and intense enhancement of the posterior pituitary, pituitary stalk, and hypothalamus. We diagnosed infundibuloneurohypophysitis associated with pSS. Hormonal replacement was started immediately and MMF was introduced without corticosteroids. After 9 months of treatment, MRI of the pituitary revealed a complete regression of the nodular thickening of the pituitary stalk, with normal enhancement and appearance of the pituitary. The pituitary axes had completely recovered, whereas the diabetes insipidus was partially restored. Our findings suggest that MMF is an effective alternative to corticosteroids for the treatment of lymphocytic hypophysitis associated with an autoimmune disease. Furthermore, this report could contribute to extend the spectrum of the neurological and endocrinological manifestations of pSS.

Topics: Autoimmune Hypophysitis; Diabetes Insipidus; Hormone Replacement Therapy; Humans; Hypopituitarism; Immunosuppressive Agents; Magnetic Resonance Imaging; Male; Middle Aged; Mycophenolic Acid; Sjogren's Syndrome

Primary Sjögren syndrome (SS) is an autoimmune disease mainly affecting the exocrine glands causing a sicca syndrome. Neurological manifestations are rarely seen in SS although they are debilitating. Peripheral neuropathies namely sensory axonal neuropathy and painful small fiber neuropathy are the most frequent neurological manifestations. Sensory neuronopathy (SN) is less frequently seen although leading to more severe handicap.The aim of the study was to analyze the clinical presentation and treatment efficacy in a series of SS-related SN.We retrospectively studied patients with SS fulfilling the American-European Classification Criteria and SN according to recent criteria. Studied variables were neurological findings, associated autoimmune diseases, biological profiles, nerve conduction and sensory/motor amplitudes study, treatments received, and outcomes. Handicap scores were studied at beginning and end of each treatment using the modified Rankin Scale (mRS).Thirteen patients were included (12 women, 1 man; median age 55 years at SN diagnosis) presenting with SN with a median follow-up of 3 years (range 2-17). In 11 patients, SN preceded or coincided with SS diagnosis. Most common neurological findings were ataxia and areflexia followed by paresthesia and pain. Lower limbs were more affected than upper limbs, neurological deficits were often symmetric and cranial nerves were affected in 3 patients. Seven patients were treated with corticosteroids, 7 with mycophenolate mofetil, 6 with hydroxychloroquine, 5 with intravenous immunoglobulins, 4 with cyclophosphamide, and 2 patients received other immunosuppressive drugs. At the beginning and at the end of follow-up, average mRS was 2.15 (median 2) and 2.38 (median 2), respectively.SS-related SN progression is heterogeneous but tends to be chronic, insidious, and debilitating despite treatment. From these data concerning a small number of patients, treatment strategies with corticosteroids in association with immunosuppressive drugs, namely mycophenolate mofetil, had positive results. In contrast, intravenous immunoglobulins had disappointing results.

Topics: Adrenal Cortex Hormones; Adult; Aged; Cyclophosphamide; Disability Evaluation; Enzyme Inhibitors; Female; Follow-Up Studies; Humans; Hydroxychloroquine; Immunoglobulins, Intravenous; Immunologic Factors; Male; Middle Aged; Mycophenolic Acid; Peripheral Nervous System Diseases; Retrospective Studies; Sensory Receptor Cells; Sjogren's Syndrome; Treatment Outcome; Young Adult

Topics: Aged; Drug Therapy, Combination; Enzyme Inhibitors; Female; Hepatitis E; Hepatitis E virus; Hepatitis, Chronic; Humans; Immunocompromised Host; Immunologic Factors; Mycophenolic Acid; Rituximab; Sjogren's Syndrome

Topics: Chronic Disease; Diagnosis, Differential; Female; Granuloma, Lethal Midline; Humans; Immunocompromised Host; Leishmania; Leishmaniasis, Cutaneous; Lupus Erythematosus, Systemic; Lymphoma, T-Cell, Cutaneous; Middle Aged; Mycophenolic Acid; Nose Diseases; Opportunistic Infections; Prednisone; Sjogren's Syndrome; Skin Ulcer

Cryoglobulinemic vasculitis is extremely rare in patients with systemic sclerosis (SSc). So far, only two cases of cryoglobulinemic vasculitis in SSc were described in the literature. This report is about a patient with SSc and secondary Sjőgren's syndrome, who developed typical clinical features of small-vessel vasculitis, including arthritis, purpura, microhaematuria, gangrene of fingers, and toes and myocardial ischemia, in the presence of mixed cryoglobulinemia, ANA, rheumatoid factor, and anti-SSA/Ro antibodies. Symptoms and signs of vasculitis worsened despite initial treatment with corticosteroids and cyclophosphamide, but improved significantly when mycophenolate mofetil was used instead cyclophosphamide.

Topics: Adrenal Cortex Hormones; Aged; Cryoglobulinemia; Cyclophosphamide; Drug Substitution; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Scleroderma, Diffuse; Sjogren's Syndrome; Treatment Outcome; Vasculitis

Topics: Adult; Antibodies, Monoclonal, Murine-Derived; Antirheumatic Agents; Drug Therapy, Combination; Dyspnea; Glucocorticoids; Humans; Hydroxychloroquine; Immunologic Factors; Lung Diseases, Interstitial; Lupus Erythematosus, Systemic; Male; Mycophenolic Acid; Prednisolone; Respiratory Function Tests; Rituximab; Sjogren's Syndrome; Treatment Outcome

Hypokalemic paralysis is a rare presentation of Fanconi syndrome (FS) caused by Sjögren Syndrome (SS). We describe a 39-year-old man who manifested flaccid paralysis of 4 limbs. Laboratory investigations showed profound hypokalemia (1.6 mmol/L) with renal K wasting, hyperchloremic metabolic acidosis with positive urine anion gap, hypophosphatemia with hyperphosphaturia, hypouricemia with hyperuricosuria, normoglycemic glycosuria, and abnormal serum creatinine concentration 2.2 mg/dL. A thorough survey for the cause of FS revealed that he had xerophthalmia and xerostomia accompanied by high anti-Ro antibody, positive Schirmer test, and delayed saliva excretion on sialoscintigraphy, confirming the diagnosis of SS. Potassium citrate, active vitamin D3, and high phosphate diet for his FS coupled with mycophenolate mofetil for SS resolved clinical symptoms and ameliorated renal function. Early recognition of HP due to the underlying SS-related FS with prompt therapy not only could terminate potentially life-threatening hypokalemia, but also improve renal outcome.

Topics: Adult; Antirheumatic Agents; Fanconi Syndrome; Humans; Hypokalemia; Male; Muscle Hypotonia; Mycophenolic Acid; Paralysis; Sjogren's Syndrome

Autoimmune autonomic ganglionopathy is a disorder of isolated autonomic failure associated with antibodies to the nicotinic acetylcholine receptor of the autonomic ganglia resulting in severe orthostatic intolerance, syncope, constipation, gastroparesis, urinary retention, dry mouth, dry eyes, blurred vision and anhidrosis. We report the autonomic test results, antibody titers and clinical findings in 8 patients with antibodies to the nicotinic acetylcholine receptor of the autonomic ganglia. There was a sigmoidal relation between the antibody titers and the fall in systolic blood pressure (r(2)=0.84). The threshold occurred with antibody titers of approximately 1 nmol/l. Over the linear portion of the sigmoid curve, with antibody titers in the 1-3 nmol/l range, increasing antibody titers resulted in more severe orthostatic hypotension (r=0.94, P<0.001). The saturation point of the sigmoidal relation occurred at approximately 3 nmol/l with drops in systolic blood pressure of approximately 100 mmHg during upright tilt. The antibody titers correlated inversely with the Valsalva ratio (r=-0.87, P<0.001), the 30:15 ratio (r=-0.84, P<0.001) and the expiratory to inspiratory ratio (r=-0.67, P<0.01). Patients with orthostatic intolerance, anhidrosis, constipation, urinary dysfunction, sicca syndrome and pupillary dysfunction had higher antibody titers than subjects that did not (P<0.01 in all cases). Autoimmune autonomic ganglionopathy is a clinically heterogeneous disease with variable presentation, particularly in subjects with lower antibody titers. Our data suggest that patients with higher antibody titers have wide spread dysautonomia while those with lower antibody levels may present with, or evolve into, more focal or restricted presentations.

Topics: Adult; Autoantibodies; Autoantigens; Autoimmune Diseases of the Nervous System; Constipation; Disease Progression; Female; Ganglia, Autonomic; Humans; Hypohidrosis; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Phenotype; Postural Orthostatic Tachycardia Syndrome; Prednisone; Primary Dysautonomias; Pupil Disorders; Receptors, Nicotinic; Shy-Drager Syndrome; Sjogren's Syndrome; Urination Disorders

A 49-year-old woman with a 1-year history of Sjögren's syndrome was diagnosed with cutaneous leukocytoclastic vasculitis and necrotizing crescentic membranous glomerulonephritis. Antineutrophil cytoplasmic antibodies targeting myeloperoxidase were found. She reported a transient episode of nephritis 4 years earlier. This pattern of kidney disease is not typical of Sjögren's syndrome. Methylprednisolone boluses followed by oral glucocorticoid therapy were given in combination with mycophenolate mofetil. Renal function stabilized after 2 months, and tests for anti-myeloperoxidase reverted to negative.

Topics: Administration, Oral; Antibodies, Antineutrophil Cytoplasmic; Drug Therapy, Combination; Female; Glomerulonephritis, Membranous; Glucocorticoids; Humans; Immunosuppressive Agents; Injections, Intravenous; Methylprednisolone; Middle Aged; Mycophenolic Acid; Peroxidase; Sjogren's Syndrome; Treatment Outcome; Vasculitis, Leukocytoclastic, Cutaneous