Mechanistic insights into anti-inflammatory and immunosuppressive effects of plant secondary metabolites and their therapeutic potential for rheumatoid arthritis.

The anti-inflammatory and immunosuppressive activities of plant secondary metabolites are due to their diverse mechanisms of action against multifarious molecular targets such as modulation of the complex immune system associated with rheumatoid arthritis (RA). This review discussed and critically analyzed the potent anti-inflammatory and immunosuppressive effects of several phytochemicals and their underlying mechanisms in association with RA in experimental studies, including preliminary clinical studies of some of them. A wide range of phytochemicals including phenols, flavonoids, chalcones, xanthones, terpenoids, alkaloids, and glycosides have shown significant immunosuppressive and anti-inflammatory activities in experimental RA models and a few have undergone clinical trials for their efficacy and safety in reducing RA symptoms and improve patient outcomes. These phytochemicals have potential as safer alternatives to the existing drugs in the management of RA, which possess a wide range of serious side effects. Sufficient preclinical studies on safety and efficacy of these phytochemicals must be performed prior to proper clinical studies. Further studies are needed to address the barriers that have so far limited their human use before the therapeutic potential of these plant-based chemicals as anti-arthritic agents in the treatment of RA is fully realized.

Systemic treatments for atopic dermatitis (eczema): Systematic review and network meta-analysis of randomized trials.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin condition with multiple systemic treatments and uncertainty regarding their comparative impact on AD outcomes. OBJECTIVE: We sought to systematically synthesize the benefits and harms of AD systemic treatments. METHODS: For the 2023 American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters AD guidelines, we searched MEDLINE, EMBASE, CENTRAL, Web of Science, and GREAT databases from inception to November 29, 2022, for randomized trials addressing systemic treatments and phototherapy for AD. Paired reviewers independently screened records, extracted data, and assessed risk of bias. Random-effects network meta-analyses addressed AD severity, itch, sleep, AD-related quality of life, flares, and harms. The Grading of Recommendations Assessment, Development and Evaluation approach informed certainty of evidence ratings. This review is registered in the Open Science Framework (https://osf.io/e5sna). RESULTS: The 149 included trials (28,686 patients with moderate-to-severe AD) evaluated 75 interventions. With high-certainty evidence, high-dose upadacitinib was among the most effective for 5 of 6 patient-important outcomes; high-dose abrocitinib and low-dose upadacitinib were among the most effective for 2 outcomes. These Janus kinase inhibitors were among the most harmful in increasing adverse events. With high-certainty evidence, dupilumab, lebrikizumab, and tralokinumab were of intermediate effectiveness and among the safest, modestly increasing conjunctivitis. Low-dose baricitinib was among the least effective. Efficacy and safety of azathioprine, oral corticosteroids, cyclosporine, methotrexate, mycophenolate, phototherapy, and many novel agents are less certain. CONCLUSIONS: Among individuals with moderate-to-severe AD, high-certainty evidence demonstrates that high-dose upadacitinib is among the most effective in addressing multiple patient-important outcomes, but also is among the most harmful. High-dose abrocitinib and low-dose upadacitinib are effective, but also among the most harmful. Dupilumab, lebrikizumab, and tralokinumab are of intermediate effectiveness and have favorable safety.

Current treatment of systemic lupus erythematosus: a clinician's perspective.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Its variable course makes it difficult to standardize patient treatment. This article aims at a literature review on available drugs for treating SLE and on drugs that have shown therapeutic effects in this disease. The PubMed/MEDLINE electronic search engine was used to identify relevant studies. This review presents the current therapeutic options, new biological therapies, and combination therapies of biologics with standard immunosuppressive and immunomodulating drugs. We have also underlined the importance to implement the treat-to-target strategy aimed at reducing or discontinuing therapy with glucocorticosteroids (GCs). The awareness of the benefits and risks of using GCs helps in refining their dosage and thereby obtaining a better safety profile. The advent of biological targeted therapies, and more recently, low-molecular-weight compounds such as kinase inhibitors, initiated numerous clinical trials in SLE patients and led to the approval of two biological drugs, belimumab, and anifrolumab, for SLE treatment. Progress in the treatment of SLE was reflected in the 2019 and 2021 recommendations of the European Alliance of Associations for Rheumatology (EULAR). However, a mass of recent clinical research data requires continuous consolidation to optimize patient outcomes.

Use of Complementary and Alternative Medicine in Patients with Autoimmune Bullous Dermatoses: A Cohort Study Analysis of a Rare Disease Group.

INTRODUCTION: Autoimmune bullous diseases (AIBD) are a heterogeneous group of rare autoantibody-mediated blistering dermatoses of the skin and/or mucous membranes. Their incidence is around 20 new cases per million inhabitants per year in Germany. Patients with chronic, oncological, or rare diseases often urge for a holistic therapeutic approach that includes complementary and alternative medicine (CAM). So far, only few contradictory reports on CAM in pemphigoid or pemphigus disease exist. The purpose of this study was to determine the frequency, motives, and satisfaction with the use of alternative treatments in patients with AIBD and to provide a basis for further investigation. METHODS: We used a structured online questionnaire, consisting of 20 questions to survey patients with AIBD and their relatives. The German pemphigus and pemphigoid self-help groups were responsible for distributing anonymized questionnaires. In total, we recovered 97 questionnaires, 63 of which met full inclusion criteria (24 males and 39 females). RESULTS: Of the included participants, more than half had a currently active disease. Of all patients, 58.7% stated that they had used CAM at least once. Women were more likely to use CAM, whereas age and education showed no association to CAM use. The main motives for using CAM were "doing something for oneself" and "opportunity to contribute to treatment" (38.1% each). The internet (23.8%) was the most common source of information, and vitamins were the most frequently used therapy (49.2%). CONCLUSION: Our results provide new insights into the demand for CAM within this rare disease patient group. Physicians should be aware of these methods to meet patient needs but also be able to identify potential barriers such as risks and interactions.

Plant Derived Immunomodulators; A Critical Review.

The concept of immunomodulation was proposed by Edward Jenner, while working on polio vaccine in 1796. Many of the autoimmune diseases such as rheumatoid arthritis, inflammatory bowel diseases, psoriatic arthritis and system lupus erythematosus, viral diseases and, some cancers are characterized with elevated levels of "immunocytokine" gene expression, including, tumor necrosis factor-α, various interleukins, cytotoxic T-cell antigen-4, B-cell activating factor. For the treatment of these diseases, the immunologically-based therapies play the major role. In these lines, the usage of phytomedicines as immunostimulants/ immunosuppressants have been enhanced considerably in last few decades and also used as a prophylactic treatment for various ailments. Phytochemicals such as flavonoids, terpenoids, polysaccharides, lactones, alkaloids, glycosides and saponins present in several plants, have been confirmed to exhibit immunomodulating properties. This review focuses on the traditional plants and their constituents which have been extensively used as immunomodulators. We have also highlighted the mechanism of action of these plant constituents related to autophagy and adjuvanticity of drugs.

[Research Advance in Treatment of Thrombotic Thrombocytopenic Purpura --Review].

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy, in which a severe deficiency of von Willebrand factor lyase results in thrombocytopenic clots that block blood vessels and eventually lead to terminal organ failure. Therapeutic plasma exchange is the cornerstone of TTP treatment which can greatly improves the survival rate of the patients. With the further exploration to the pathophysiological mechanism of TTP, other alternative therapies, new immunosuppressive agents, targeted antagonists, gene therapy and other emerging means gradually emerge, which are expected to further reduce the mortality and recurrence rate of the patients. In this review, the new developments in TTP treatment were summarized briefly.

The role of concomitant immunosuppressants in impeding the progression of diabetic retinopathy: A pilot study.

PURPOSE: Hallmark of Diabetic Retinopathy (DR) is blood-retinal barrier alteration. Vascular endothelial growth factor (VEGF) and inflammation are involved in the pathogenesis of DR. Anti-VEGFs and lasers are effective in treating DR but have numerous drawbacks, hence the need to develop alternative therapies that may delay the onset or progression of DR. METHODS: Fifteen patients were recruited in each group; the study group was on immunosuppressants for some other coexisting disease and the control group was not on them. Each subject underwent detailed history, ophthalmic examination, and glycosylated hemoglobin (HbA1c) and renal function tests at the time of recruitment and the end of one year. Primary outcome measure was to compare the progression of DR in diabetics on immunosuppressant versus those not on it. RESULTS: Median age in the study and control group was 57 years and 60 years, respectively (P = 0.6). Median duration of diabetes was 11 and 12 years in the study and control group, respectively (P = 0.7). HbA1c for the study and control group for first visit was 7.6% and 8.0%, respectively (P = 0.26) and for second visit was 7.5% and 8.1%, respectively (P = 0.11). Hypertensives in the study and control groups were 9 and 4, respectively (P = 0.065); renal disease in the study and control groups was 4 and 2, respectively (P = 0.361). The control group showed 33.3% progression of DR, and no progression was seen in the study group (P = 0.014). CONCLUSION: Immunosuppressants seemed to delay the onset and progression of DR in the earlier stages.

Folinate Supplementation Ameliorates Methotrexate Induced Mitochondrial Formate Depletion In Vitro and In Vivo.

(1) Background: Antifolate methotrexate (MTX) is the most common disease-modifying antirheumatic drug (DMARD) for treating human rheumatoid arthritis (RA). The mitochondrial-produced formate is essential for folate-mediated one carbon (1C) metabolism. The impacts of MTX on formate homeostasis in unknown, and rigorously controlled kinetic studies can greatly help in this regard. (2) Methods: Combining animal model (8-week old female C57BL/6JNarl mice, n = 18), cell models, stable isotopic tracer studies with gas chromatography/mass spectrometry (GC/MS) platforms, we systematically investigated how MTX interferes with the partitioning of mitochondrial and cytosolic formate metabolism. (3) Results: MTX significantly reduced de novo deoxythymidylate (dTMP) and methionine biosyntheses from mitochondrial-derived formate in cells, mouse liver, and bone marrow, supporting our postulation that MTX depletes mitochondrial 1C supply. Furthermore, MTX inhibited formate generation from mitochondria glycine cleavage system (GCS) both in vitro and in vivo. Folinate selectively rescued 1C metabolic pathways in a tissue-, cellular compartment-, and pathway-specific manner: folinate effectively reversed the inhibition of mitochondrial formate-dependent 1C metabolism in mouse bone marrow (dTMP, methionine, and GCS) and cells (dTMP and GCS) but not methionine synthesis in liver/liver-derived cells. Folinate failed to fully recover hepatic mitochondrial-formate utilization for methionine synthesis, suggesting that the efficacy of clinical folinate rescue in MTX therapy on hepatic methionine metabolism is poor. (4) Conclusion: Conducting studies in mouse and cell models, we demonstrate novel findings that MTX specifically depletes mitochondrial 1C supply that can be ameliorated by folinate supplementation except for hepatic transmethylation. These results imply that clinical use of low-dose MTX may particularly impede 1C metabolism via depletion of mitochondrial formate. The MTX induced systematic and tissue-specific formate depletion needs to be addressed more carefully, and the efficacy of folinate with respect to protecting against such depletion deserves to be evaluated in medical practice.

Immunosuppressant quantification in intravenous microdialysate - towards novel quasi-continuous therapeutic drug monitoring in transplanted patients.

OBJECTIVES: Therapeutic drug monitoring (TDM) plays a crucial role in personalized medicine. It helps clinicians to tailor drug dosage for optimized therapy through understanding the underlying complex pharmacokinetics and pharmacodynamics. Conventional, non-continuous TDM fails to provide real-time information, which is particularly important for the initial phase of immunosuppressant therapy, e.g., with cyclosporine (CsA) and mycophenolic acid (MPA). METHODS: We analyzed the time course over 8 h of total and free of immunosuppressive drug (CsA and MPA) concentrations measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in 16 kidney transplant patients. Besides repeated blood sampling, intravenous microdialysis was used for continuous sampling. Free drug concentrations were determined from ultracentrifuged EDTA-plasma (UC) and compared with the drug concentrations in the respective microdialysate (µD). µDs were additionally analyzed for free CsA using a novel immunosensor chip integrated into a fluorescence detection platform. The potential of microdialysis coupled with an optical immunosensor for the TDM of immunosuppressants was assessed. RESULTS: Using LC-MS/MS, the free concentrations of CsA (fCsA) and MPA (fMPA) were detectable and the time courses of total and free CsA comparable. fCsA and fMPA and area-under-the-curves (AUCs) in µDs correlated well with those determined in UCs (r≥0.79 and r≥0.88, respectively). Moreover, fCsA in µDs measured with the immunosensor correlated clearly with those determined by LC-MS/MS (r=0.82). CONCLUSIONS: The new microdialysis-supported immunosensor allows real-time analysis of immunosuppressants and tailor-made dosing according to the AUC concept. It readily lends itself to future applications as minimally invasive and continuous near-patient TDM.

Oral mycophenolate mofetil as a stabilizing treatment for progressive non-segmental vitiligo: results from a prospective, randomized, investigator-blinded pilot study.

Dexamethasone oral mini-pulse (OMP) is commonly used to halt progression of non-segmental vitiligo (NSV). There is an unmet need for non-phototherapy, non-corticosteroid therapeutic options for stabilizing actively spreading NSV. To assess the efficacy of oral mycophenolate mofetil in stabilizing active NSV in comparison to OMP. In this prospective, randomized, investigator-blinded study, 50 patients of active vitiligo [baseline vitiligo disease activity (VIDA) score 4] were randomized into two groups in 1:1 ratio. Group A received oral dexamethasone (2.5 mg on two successive days a week) and group B received mycophenolate mofetil (up to 2 g) for 180 days with a treatment-free follow-up period of 90 days. Assessment was done using VIDA, number of new lesions in past 30 days, and Vitiligo Area Scoring Index (VASI). Arrest of disease progression was defined as the absence of any new lesions in past 30 days. Twenty-five patients received OMP (group A, 11 males, 14 females), and 25 received mycophenolate (group B, 12 males, 13 females). In both groups, Kruskal-Wallis revealed a significant trend for reduction in VIDA and the number of new lesions in last 30 days, over the treatment and follow-up duration when compared to baseline (p < 0.001). The first significant reduction in VIDA was noticed on 90th day in groups A and B (p < 0.001). In both groups, VIDA reduced significantly at the 180th day compared to baseline (p < 0.001, WMP), only to increase significantly at the 270th day (p < 0.001, WMP). VIDA in group B was marginally higher at 270 days than group A (p 0.03; Mann-Whitney). Eighteen and 17 patients achieved VIDA 2 + on the 180th day in groups A and B, respectively. The mean number of new lesions in last 30 days reduced significantly in both groups at the 180th day (p < 0.001) and 270th day [p < 0.001; Wilcoxon matched pairs (WMP)] when compared to baseline; but increased significantly at the 270th day compared to the 180th day (p 0.006 WMP). Twenty patients in group A and 18 patients in group B had arrest of the disease activity with treatment. Mean duration to arrest disease progression was 47.2 ± 12.1 days in group A, and 52.5 ± 9.3 days in group B; p 0.21. The difference between VASI at baseline and VASI at the 180 and 270th days was non-significant in both groups (p 0.18 WMP). Five patients in each group failed the respective treatments. Acne (n = 3), weight gain (n = 3), headache, insomnia and menstrual irregularity (n = 1 each) were the important adverse effects noted with dexamethasone pulse; whereas nausea (n = 6) and diarrhea (n = 4) were the commonest adverse effects noted with mycophenolate. Two patients in group B discontinued treatment because of leucopenia (n = 1) and transaminitis (n = 1) that resolved after the discontinuation of mycophenolate. Both OMP and mycophenolate mofetil halt actively spreading vitiligo, and have distinct adverse effect profiles. These should be offered in progressive vitiligo, especially in circumstances precluding the use of phototherapy. Relapse occurred significantly earlier with mycophenolate, and relapse rate was higher (though non-significant) than dexamethasone OMP. The repigmentation potential is minimal for both therapies. This study was approved by Institute Ethics Committee, and retrospectively registered with clinical trial registry of India (CTRI/2018/02/011,664).

Cytokine Storm in Novel Coronavirus Disease (COVID-19): Expert Management Considerations.

AIM/OBJECTIVE/INTRODUCTION: Cytokine storm or cytokine release syndrome (CRS) is inevitable in severe and critically ill patients with novel coronavirus disease-2019 (COVID-19). This review aimed to discuss current therapeutic options for the management of CRS in COVID-19. BACKGROUND: Cytokine storm is caused by the colossal release of proinflammatory cytokines [e.g., IL (interleukin)-2, IL-6, IL-8 TNF (tumor necrosis factor)-α, etc.] causing dysregulated, hyperimmune response. This immunopathogenesis leads to acute lung injury and acute respiratory distress syndrome (ARDS). Targeting cytokine storm with the therapies that are already available in India with the support of published guidelines and consensus can assist in achieving a better outcome in COVID-19. REVIEW RESULTS: We predominantly included published guidelines or consensus recommendations about the management of cytokine storm in COVID-19. From the existing literature evidence, it is observed that among the currently available agents, low-dose corticosteroids and heparin can be beneficial in managing cytokine storm. The use of serine protease inhibitors such as ulinastatin has been advised by some experts. Though therapies such as high-dose vitamin C and interleukin-6 inhibitors (e.g., tocilizumab) have been advised, the evidence regarding their use for cytokine storm in COVID-19 is limited. Therapies such as Janus kinase inhibitors (JAK) inhibitors and Neurokinin-1 receptor (NK-1) antagonists are still in research. Besides, pharmaceutical treatments, use of blood purification strategies, and convalescent plasma may be life-saving options in some of the critically ill COVID-19 patients. For these therapies, there is a need to generate further evidence to substantiate their use in CRS management. CONCLUSION: Current management of COVID-19 is preventive and supportive. Different therapies can be used to prevent and treat the cytokine storm. More research is needed for further supporting the use of these treatments in COVID-19. HOW TO CITE THIS ARTICLE: Mehta Y, Dixit SB, Zirpe KG, Ansari AS. Cytokine Storm in Novel Coronavirus Disease (COVID-19): Expert Management Considerations. Indian J Crit Care Med 2020;24(6):429-434.

Costs and Treatment Patterns Among Patients with Atopic Dermatitis Using Advanced Therapies in the United States: Analysis of a Retrospective Claims Database.

INTRODUCTION: For many, atopic dermatitis (AD) is not adequately controlled with topical regimens. This analysis examined treatment using advanced therapies and associated costs. METHODS: The IQVIA Health Plan Claims data set was analyzed. Patients aged ≥ 12 years with AD who newly initiated advanced therapy after the availability of dupilumab (March 28, 2017) and had ≥ 6 months continuous enrollment before and after their first advanced therapy claim (index date) were included. Advanced therapies included dupilumab, systemic corticosteroids (SCSs), systemic immunosuppressants (SISs), and phototherapy. A multivariate regression model was used to predict annualized follow-up healthcare costs. RESULTS: In total, 1980 patients were included (61.1% female; mean age, 41.2 years [SD, 17.4]; 11.3% < 18 years). Pre-index date, 65.2% of patients used topical corticosteroids (TCSs; 40.7% and 32.1% used medium and high potency, respectively). The most common advanced therapy was SCSs (N = 1453 [73.4%]; 69.2% prednisone) followed by dupilumab (N = 265 [13.4%]), SISs (N = 99 [5.0%]; 47.5% methotrexate), and phototherapy (N = 163 [8.2%]). Of patients treated with dupilumab, SISs, and phototherapy, 17.4%, 26.3%, and 14.1%, respectively, were prescribed SCSs post-index date. Overall, 62.6% of patients initiating SCSs, 49.1% initiating dupilumab, 64.6% initiating SISs, and 36.2% initiating phototherapy were prescribed TCSs post-index date. Mean annualized total costs (SD) post-index date were $20,722 ($47,014): $11,196 ($41,549) in medical costs ($7973 [$35,133] in outpatient visit costs) and $9526 ($21,612) in pharmacy costs. Mean annualized total cost (SD) varied significantly (P < 0.05) by index treatment: dupilumab, $36,505 ($14,028); SCSs, $17,924 ($49,019); SISs, $24,762 ($47,583); phototherapy, and $17,549 ($57,238). CONCLUSIONS: Switching to combination therapy with SCSs and TCSs was common within 6 months of initiating advanced therapy in patients with AD. Patients also incurred significant pharmacy and outpatient costs. These results highlight the difficulty of managing AD with these existing treatment options.

ANCA-associated vasculitides: Recommendations of the French Vasculitis Study Group on the use of immunosuppressants and biotherapies for remission induction and maintenance.

Treatment of vasculitides associated with anti-neutrophil cytoplasm antibodies (ANCA) (AAVs) has evolved dramatically in recent years, particularly since the demonstration of rituximab efficacy as remission induction and maintenance therapy for granulomatosis with polyangiitis and microscopic polyangiitis. In 2013, the French Vasculitis Study Group (FVSG) published recommendations for its use by clinicians. Since then, new data have made it possible to better specify and codify prescription of rituximab to treat AAVs. Herein, the FVSG Recommendations Committee, an expert panel comprised of physicians with extensive experience in the treatment and management of vasculitides, presents its consensus guidelines based on literature analysis, the results of prospective therapeutic trials and personal experience.

Selenium-containing polysaccharides from Lentinula edodes-Biological activity.

We hypothesized that selenium(Se)-enriched polysaccharides would possess superior biological activity when compared to those non-enriched. To verify this hypothesis, we obtained by biotechnological methods a Se-enriched analog of Japanese anticancer drug lentinan and, as a reference, the non-Se-enriched fraction. We tested the effects of the obtained fractions on the proliferation of human peripheral blood mononuclear cells. The results suggested a selective immunosuppressive activity, non-typical for mushroom derived polysaccharides. Both fractions caused significant inhibition of human T lymphocyte proliferation induced by mitogens, without significant effects on B lymphocytes. The inhibitory effect was not due to the toxicity of the examined polysaccharides. In normal (HUVEC) or malignant (HeLa) cells tested fractions significantly enhanced cell viability and protected the cells from oxidative stress conditions. However, we observed no effect of the polysaccharide fractions on the production of reactive oxygen species by granulocytes in vitro. The selenium content increased the biological activity of the tested polysaccharide fractions.

[Musculoskeletal manifestations of sarcoidosis]. / Muskuloskelettale Manifestationen der Sarkoidose.

Musculoskeletal manifestations in the context of sarcoidosis are frequently observed. The rheumatologist regularly encounters this disease in clinical practice. In the present review, we aim to give a current overview of the manifestations and treatments relevant to the practicing rheumatologist. The most frequently encountered manifestation is Lofgren's syndrome, which is characterized by bilateral ankle periarthritis, bilateral hilar lymphadenopathy, and erythema nodosum and has an excellent prognosis. Chronic arthropathy most commonly manifests as oligoarthritis, which sometimes hampers its differentiation from spondylarthropathies, especially when sacroiliitis, enthesitis or dactylitis are simultaneously present. Isolated vertebral granulomas are rare and require infectious and malignant disorders to be excluded, since there are no specific imaging findings that are exclusively found in vertebral sarcoidosis. The presence of granulomas in skeletal muscle is common in muscle biopsies, whereas clinically overt myopathy is present in only around 1-2% of patients. Therapeutic responses vary among the different clinical phenotypes. Non-steroidal anti-inflammatory drugs and low to medium dose glucocorticoids are the first-line therapy for musculoskeletal manifestations and often lead to adequate disease control in acute sarcoidosis. When these are ineffective or not tolerated, steroid-sparing agents are increasingly used in chronic sarcoidosis. Evidence for all medications used in sarcoid-related arthritis is comparatively scant. When supplementing vitamin D, the possible development of hypercalcemia, even at standard doses, needs to be considered; the optimal therapeutic levels for the prevention of medication-induced osteoporosis in sarcoidosis have not been firmly established.

Scientific evidence for the use of current traditional systemic therapies in patients with hidradenitis suppurativa.

Traditional systemic therapies are frequently prescribed for the treatment of hidradenitis suppurativa (HS). Clinicians consider antibiotics, retinoids, antiandrogens, immunosuppressants, and less common treatment, such as fumarates, in the management of HS. Different classes of medications have been selected to treat HS based on their ability to target various pathways of the condition. Concerns about infection, such as infection with Clostridium difficile, necessitates switching therapy or shortening the course of therapy with specific antibiotics. This review explores the outcomes with the use of numerous medical therapies and postulates explanations for their efficacy or lack of response. Data on long-term safety and efficacy with traditional systemic therapies are lacking.

[Optic neuropathy in a case of recurrent idiopathic hypertrophic pachymeningitis unresponsive to steroids and immunosuppressants]. / Neuropatía óptica en un caso de paquimeningitis hipertrófica idiopática recurrente sin respuesta a esteroides e inmunosupresores.

CASE REPORT: A 38-year-old female patient with bilateral papilledema who presented with loss of vision in her left eye. The Magnetic Resonance Imagining (MRI) showed thickening of the dura mater, and the intracranial pressure was elevated. A cancer, infectious, and autoimmune origin was ruled out. DISCUSSION: The initial response to high doses of corticoids was satisfactory, with disappearance of the optic disc enema, with visual acuity and an improvement in the MRI. However, after one year without treatment she had a new outbreak of the disease. Despite renewed treatment with corticoids and azathioprine, the patient developed a left optic neuropathy and irreversible visual loss.

[Management of chronic hand eczema]. / Prise en charge de l'eczéma chronique des mains.

The management of hand eczema, more readily called chronic hand dermatitis, is complex. This heaviness is related not only to the disease itself by its different clinical forms but also the multiplicity and diversity of etiological factors, triggering / maintaining or aggravating factors. The repeated therapeutic failures are ransom of incorrect information about the disease and its environment, a lack of clarity in the prescription and duration of treatment in general too short. The reference treatment is high potency topical steroids with or without occlusion for 4-8 weeks followed by alitretinoin 30 mg / day for at least 3-6 months with a monthly lipid and liver monitoring and mandatory monthly pregnancy test in women of childbearing. Associated measures and patient education are the cornerstones of successful treatment. Other alternative treatments such as phototherapy, methotrexate, cyclosporin, mycophenolate mofetil etc. can be considered in case of resistance or for clearing followed by topical treatments.