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BMJ Case Reports Sep 2023A male in his 60s developed a pruritic, maculopapular rash on his torso and arms, sparing his palms and soles. He tested positive for ANA and an initial skin biopsy...
A male in his 60s developed a pruritic, maculopapular rash on his torso and arms, sparing his palms and soles. He tested positive for ANA and an initial skin biopsy identified "bullous lupus," supporting the diagnosis of a connective tissue disease. Additional symptoms included headaches, facial nerve palsy and hearing loss, which partially responded to oral corticosteroids. He subsequently developed a steroid-dependent left eye scotoma, neuroretinitis and optic nerve papillitis. Mycophenolate mofetil was added but an attempted oral steroid taper led to a worsening rash, progressive retinitis and papillitis. Neurosyphilis was confirmed by serum positive rapid plasma reagin test, reactive treponema pallidum antibodies, positive cerebrospinal fluid venereal disease research laboratory and positive spirochete immunostain of skin biopsy of lesional (rash) tissue. Treatment with intravenous ceftriaxone resolved his rash and visual symptoms. It is important to consider syphilis as a mimicker of connective tissue diseases.
Topics: Humans; Male; Neurosyphilis; Syphilis; Papilledema; Connective Tissue Diseases; Exanthema; Treponema pallidum
PubMed: 37770241
DOI: 10.1136/bcr-2023-256301 -
Zeitschrift Fur Rheumatologie Feb 2024This study aimed to assess the relative efficacy and safety of calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), and azathioprine (AZA) as maintenance therapies... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aimed to assess the relative efficacy and safety of calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), and azathioprine (AZA) as maintenance therapies for lupus nephritis.
METHODS
Randomized controlled trials (RCTs) examining the efficacy and safety of CNI, MMF, and AZA as maintenance therapies in patients with lupus nephritis were included. We performed a Bayesian random-effects network meta-analysis to combine the direct and indirect evidence from RCTs.
RESULTS
Ten RCTs comprising 884 patients were included in the study. Although the difference was not statistically significant, MMF showed a trend toward a lower relapse rate compared with AZA (odds ratio [OR] 0.72, 95% credible interval [CrI] 0.45-1.22). Similarly, tacrolimus showed a trend toward a lower relapse rate compared with AZA (OR 0.85, 95% CrI 0.34-2.00). Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that MMF had the highest probability of being the best treatment based on the relapse rate, followed by CNI and AZA. The incidence of leukopenia in the MMF and CNI groups was significantly lower than that in the AZA group (OR 0.12, 95% CrI 0.04-0.34; OR 0.16, 95% CrI 0.04-0.50; respectively). Fewer patients with infections were observed in the MMF group than in the AZA group, although the difference was not statistically significant. The analysis of withdrawals due to adverse events showed a similar pattern.
CONCLUSION
Lower relapse rates combined with a more favorable safety profile suggest that CNI and MMF are superior to AZA as maintenance treatments in lupus nephritis patients.
Topics: Humans; Azathioprine; Mycophenolic Acid; Lupus Nephritis; Immunosuppressive Agents; Calcineurin Inhibitors; Network Meta-Analysis; Treatment Outcome; Recurrence
PubMed: 37278824
DOI: 10.1007/s00393-023-01374-x -
Current Opinion in Nephrology and... May 2024As the most common primary glomerulonephritis, immunoglobulin A (IgA) nephropathy (IgAN) is an important cause of kidney failure and mortality. Until recently,... (Review)
Review
PURPOSE OF REVIEW
As the most common primary glomerulonephritis, immunoglobulin A (IgA) nephropathy (IgAN) is an important cause of kidney failure and mortality. Until recently, therapeutic options were limited. Fortunately, there have been numerous recent clinical trials demonstrating efficacy of new therapies in slowing chronic kidney disease (CKD) progression at varying stages of disease.
RECENT FINDINGS
The TESTING trial has provided high-quality evidence for slowing estimated glomerular filtration rate (eGFR) decline with a reduced-dose glucocorticoid regimen, while demonstrating an improved safety profile. Targeted-release budesonide represents a well tolerated therapy for reducing eGFR decline. Mycophenolate mofetil may reduce CKD progression in some populations, while hydroxychloroquine is efficacious in reducing proteinuria. Sodium-glucose cotransporter (SGLT2) inhibitors and sparsentan are effective therapies for CKD due to IgAN, but should not be used in lieu of disease-modifying immunosuppressive therapy. Many new therapies are approaching readiness for clinical use.
SUMMARY
Numerous therapeutic options now exist and include disease-modifying and nephroprotective drugs. Identifying the right treatment for the right patient is now the clinical challenge and, with new drugs on the horizon, represents the primary unmet research need in this rapidly-developing field.
Topics: Humans; Glomerulonephritis, IGA; Standard of Care; Renal Insufficiency, Chronic; Mycophenolic Acid; Glucocorticoids; Proteinuria
PubMed: 38411173
DOI: 10.1097/MNH.0000000000000979 -
International Journal of Molecular... Jun 2024Allogeneic hematopoietic stem cell transplantation has become a treatment option for otherwise non-curative conditions, both malignant and benign, affecting children and... (Review)
Review
Allogeneic hematopoietic stem cell transplantation has become a treatment option for otherwise non-curative conditions, both malignant and benign, affecting children and adults. Nevertheless, the latest research has been focusing extensively on transplantation from related and unrelated haploidentical donors, suitable for patients requiring emergent hematopoietic stem cell transplantation (HSCT) in the absence of an HLA-matched donor. Haploidentical HSCT (haplo-HSCT) can be an effective treatment for non-malignant pediatric disorders, such as primary immunodeficiencies or hemoglobinopathies, by enabling a much quicker selection of the appropriate donor for virtually all patients, low incidence of graft-versus-host disease (GVHD), and transplant-related mortality (TRM). Moreover, the outcomes of haplo-HSCT among children with hematological malignancies have improved radically. The most demanding tasks for clinicians are minimizing T-cell-mediated alloreactivity as well as early GVHD prevention. As a result, several T-cell depletion approaches, such as ex vivo T-cell depletion (TCD), and T-cell replete approaches, such as a combination of anti-thymocyte globulin (ATG), post-transplantation cyclophosphamide (PTCy), cyclosporine/tacrolimus, mycophenolate mofetil, or methotrexate, have been taken up. As more research is needed to establish the most beneficial form of therapy, haplo-HSCT is currently considered an alternative donor strategy for pediatric and adult patients with complications like viral and bacterial infections, invasive fungal disease, and GVHD.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Child; Graft vs Host Disease; Transplantation, Haploidentical; Hematologic Diseases; Transplantation Conditioning
PubMed: 38928087
DOI: 10.3390/ijms25126380 -
Skin Appendage Disorders Feb 2024Lichen planopilaris (LPP) is an autoimmune disorder leading to lymphocytic cicatricial alopecia. Different agents such as hydroxychloroquine, methotrexate, cyclosporine,... (Review)
Review
BACKGROUND
Lichen planopilaris (LPP) is an autoimmune disorder leading to lymphocytic cicatricial alopecia. Different agents such as hydroxychloroquine, methotrexate, cyclosporine, and mycophenolate mofetil have been tried to control hair loss with limited efficacy. JAK inhibitors are immune-modulating drugs which interfere with the JAK-STAT signaling pathway in lymphocytes and are used in treatment of inflammatory conditions such as rheumatoid arthritis and alopecia areata.
SUMMARY
Our aim was to determine effectiveness of JAK inhibitors in LPP and its clinical variant, frontal fibrosing alopecia. A literature search was conducted using PubMed, Google Scholar, and Cochrane databases. A total of 7 articles describing 35 patients were found. Although data on treatment are limited to retrospective studies and case reports, JAK inhibitors can be considered a new therapeutic option, especially in recalcitrant cases. Large prospective studies and randomized control trials are needed to provide further evidence supporting efficacy.
KEY MESSAGES
Besides the fact that data on the treatment of LPP and FFA with JAK inhibitors are limited to retrospective studies and case reports, but JAK inhibitors can be considered as a new therapeutic option especially in recalcitrant cases.
PubMed: 38313572
DOI: 10.1159/000534631 -
Dermatology (Basel, Switzerland) 2024Treatment of vitiligo seeks to achieve three goals: cessation of disease progression, regeneration of pigmentation, and prevention of recurrence. (Review)
Review
BACKGROUND
Treatment of vitiligo seeks to achieve three goals: cessation of disease progression, regeneration of pigmentation, and prevention of recurrence.
SUMMARY
Number of nonsurgical interventions are available that suppress the autoimmune response and regenerate the melanocytes from the reservoir: phototherapy including psoralen and ultraviolet A, narrowband ultraviolet B, and 308-nm excimer and 311-nm Titanium:Sapphire lasers; topical agents including topical calcineurin inhibitors, topical corticosteroids, and topical 5-fluorouracil; and systemic agents including corticosteorids, mycophenolate mofetil, cyclosporine, methotrexate, minocycline, afamelanotide, and antioxidants. In recent years, a great advance has been made in the understanding of pathogenesis of vitiligo, and JAK inhibitors are being investigated as a new treatment. Minimally invasive procedures such as fractional lasers or microneedling can help achieve the optimal treatment outcome when used properly.
KEY MESSAGES
Our review describes various treatment modalities for vitiligo based on their molecular mechanism of action. Bridging the gap between molecular mechanisms and therapeutic options would be a valuable reference for physicians in clinical practice.
Topics: Vitiligo; Humans; Dermatologic Agents; Janus Kinase Inhibitors; Calcineurin Inhibitors; Ultraviolet Therapy; Phototherapy; Laser Therapy; Immunosuppressive Agents
PubMed: 38417409
DOI: 10.1159/000537810 -
Multiple Sclerosis (Houndmills,... Mar 2024Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can cause optic neuritis, transverse myelitis, or acute disseminated encephalomyelitis (ADEM)....
BACKGROUND
Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can cause optic neuritis, transverse myelitis, or acute disseminated encephalomyelitis (ADEM). Immunotherapy is often used for relapsing disease, but there is variability in treatment decisions.
OBJECTIVE
The objective was to determine the annualized relapse rates (ARRs) and incidence rate ratios (IRRs) compared to pre-treatment and relapse-freedom probabilities among patients receiving steroids, B-cell depletion (BCD), intravenous immunoglobulin (IVIG), and mycophenolate mofetil (MMF).
METHODS
Retrospective cohort study of patients with relapsing MOGAD treated at Mass General Brigham. ARRs and IRRs compared to pre-treatment, and relapse-freedom probability and odds ratio for relapse-freedom compared to prednisone were calculated.
RESULTS
A total of 88 patients met the inclusion criteria. The ARR on IVIG was 0.13 (95% confidence interval (CI) = 0.06-0.27) and the relapse-freedom probability after at least 6 months of therapy was 72%. The ARR on BCD was 0.51 (95% CI = 0.34-0.77), and the relapse-freedom probability was 33%. The ARR on MMF was 0.32 (95% CI = 0.19-0.53) and the relapse-freedom probability was 49%. In pediatric-onset disease, MMF had the lowest ARRs (0.15, 95% CI = 0.07-0.33).
CONCLUSION
IVIG had the lowest ARRs and IRRs compared to pre-treatment and the highest relapse-freedom odds ratio compared to prednisone, while BCD had the lowest. In pediatric-onset MOGAD, MMF had the lowest ARRs.
Topics: Humans; Child; Myelin-Oligodendrocyte Glycoprotein; Immunoglobulins, Intravenous; Retrospective Studies; Prednisone; Autoantibodies; Neoplasm Recurrence, Local; Mycophenolic Acid; Immunotherapy; Recurrence
PubMed: 38314479
DOI: 10.1177/13524585241226830 -
The Medical Letter on Drugs and... Apr 2024
Topics: Humans; Myasthenia Gravis; Immunosuppressive Agents; Complement C5; Peptides, Cyclic
PubMed: 38576149
DOI: 10.58347/tml.2024.1700c -
Scientific Reports Aug 2023Mycophenolate mofetil (MMF) is applied in proteinuric kidney diseases, but the exact mechanism of its effect on podocytes is still unknown. Our previous in vitro...
Mycophenolate mofetil (MMF) is applied in proteinuric kidney diseases, but the exact mechanism of its effect on podocytes is still unknown. Our previous in vitro experiments suggested that MMF can ameliorate podocyte damage via restoration of the Ca-actin cytoskeleton axis. The goal of this study was to characterize podocyte biology during MMF treatment in nephrotoxic serum (NTS) nephritis (NTN). NTN was induced in three-week old wild-type mice. On day 3, half of the mice were treated with MMF (100 mg/kgBW/d p.o.) for one week. On day 10, we performed proteomic analysis of glomeruli as well as super-resolution imaging of the slit diaphragm. For multiphoton imaging of Ca concentration ([Ca]), the experimental design was repeated in mice expressing podocyte-specific Ca sensor. MMF ameliorated the proteinuria and crescent formation induced by NTS. We identified significant changes in the abundance of proteins involved in Ca signaling and actin cytoskeleton regulation, which was further confirmed by direct [Ca] imaging in podocytes showing decreased Ca levels after MMF treatment. This was associated with a tendency to restoration of podocyte foot process structure. Here, we provide evidence that MPA has a substantial direct effect on podocytes. MMF contributes to improvement of [Ca] and amelioration of the disorganized actin cytoskeleton in podocytes. These data extend the knowledge of direct effects of immunosuppressants on podocytes that may contribute to a more effective treatment of proteinuric glomerulopathies with the least possible side effects.
Topics: Mycophenolic Acid; Animals; Mice; Podocytes; Nephritis; Mice, Inbred C57BL; Kidney Glomerulus; Proteome; Actin Cytoskeleton
PubMed: 37644089
DOI: 10.1038/s41598-023-41222-1 -
Middle East African Journal of... 2022The purpose of the study was to evaluate the efficacy and safety of systemic mycophenolate mofetil (MMF) treatment in ocular surface inflammatory diseases.
PURPOSE
The purpose of the study was to evaluate the efficacy and safety of systemic mycophenolate mofetil (MMF) treatment in ocular surface inflammatory diseases.
METHODS
For this retrospective study, patients who were treated with systemic MMF for ocular surface inflammatory diseases between March 2020 and March 2022 were evaluated. Apart from demographic data, examination notes including MMF treatment indication and systemic side effect interrogation and routine laboratory examinations during drug treatment were extracted from the patient records. Detailed staging scores were performed according to the diagnosis including Foster and Mondino for ocular mucous membrane pemphigoid (MMP) and limbal stem cell deficiency scoring for limbal transplantation. For thorough evaluation, anterior segment pictures were used.
RESULTS
Fourteen patients were enrolled to the study, with a mean age of 58 ± 12. MMP (6, 42.8%) and limbal allograft transplantation (6, 42.8%) constituted the main indications for the MMF treatment, followed by keratitis-ichthyosis-deafness (KID) syndrome (1, 7.2%) and Mooren's ulcer (1, 7.2%). Five of six patients with MMP regressed according to both staging systems. Only one remained stable which was evaluated as Stage 3. Furthermore, while all limbal transplant groups (6) stabilized and showed regression according to the individualized limbal stem cell deficiency staging system with no rejection during follow-up. Furthermore, patients with Mooren's ulcer and KID syndrome showed control of the inflammation and stabilization after MMF treatment. No significant systemic side effects apart from constipation and nausea (3) were observed in patients whose routine laboratory tests were stable throughout the follow-up.
CONCLUSION
MMF has the potential to be a valuable and safe systemic agent of first choice in the control of ocular surface inflammatory disorders, especially when topical treatment is not effective. With such studies, it is predicted that MMF may reach wider usage areas with the increase in its effectiveness and safety in its use for ocular surface inflammatory pathologies.
Topics: Humans; Middle Aged; Aged; Mycophenolic Acid; Immunosuppressive Agents; Retrospective Studies; Limbal Stem Cell Deficiency; Ophthalmologists; Ulcer; Eye Diseases; Graft Rejection
PubMed: 38162558
DOI: 10.4103/meajo.meajo_109_23