OBJECTIVE: The effectiveness of immunosuppressive and corticosteroid treatments for Immunoglobulin A (IgA) nephropathy (IgAN) remains thoroughly evaluated. We undertook a meta-analysis to investigate the efficacy and safety of low-dose corticosteroids plus leflunomide for progressive IgA nephropathy.
METHODS: Eligible studies were obtained from PubMed, Embase, and Cochrane Library databases. We also searched the references of the included studies. Our protocol followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. Eligibility criteria were defined using a PICOS framework.
RESULTS: Our study included three articles presenting 342 patient cases. Findings revealed that low-dose corticosteroids combined with the leflunomide group were effective in relieving urine protein excretion (UPE) [mean difference (MD) = -0.35, 95% confidence interval (CI): -0.41 to -0.30, P < 0.00001] compared with the full-dose corticosteroids group. Regarding serum creatinine (SCr), estimated glomerular filtration rate (eGFR), complete remission rate, and overall response rate, there was no difference between the groups (p > 0.05). Regarding safety, low-dose corticosteroids combined with leflunomide significantly reduced the risk of serious adverse events [odds ratio (OR): 0.11, 95% CI: 0.01 to 0.91, P = 0.04]. Besides, no significant differences were observed between the two groups in the incidence of respiratory infection, abnormal liver function, diarrhea, herpes zoster, alopecia, pruritus, insomnia, pneumonia, diabetes, and urinary tract infection (P > 0.05).
CONCLUSIONS: Low-dose corticosteroids combined with leflunomide are a safe and effective treatment for progressive IgA nephropathy.
BACKGROUND: The PROSPERO registration number is CRD42022361883.

Rheumatoid arthritis (RA), a chronic autoimmune disorder, is characterized by erosive inflammation of bone and cartilage, leading to progressive joint destruction. Pulmonary involvement occurs in approximately 60% of RA patients, manifests most commonly as interstitial lung disease and, less commonly, as rheumatoid lung nodules. Here, we report a 50-year-old woman, non-smoker, with recurrent cough and sputum of 7 years\' duration, accompanied by a chest CT showing multiple cavitary nodules in both lungs. She had been treated empirically at several medical centers and was finally diagnosed with rheumatoid lung nodules. Marked improvement in rheumatoid lung nodules was observed after treatment with tocilizumab in combination with glucocorticoids and leflunomide. The aim of this study was to improve clinicians\' understanding of rheumatoid lung nodules by analyzing the clinical features, diagnosis, and treatment of this case, and reviewing the relevant medical literature.
类风湿关节炎（rheumatoid arthritis，RA）是一种以侵蚀性关节炎症为主要临床表现的自身免疫病，约60%的患者可出现肺部受累，其常见表现类型为间质性肺病，类风湿肺结节少见。本文报道1例50岁女性反复咳嗽、咳痰7年伴胸部CT显示双肺多发结节伴空洞形成，辗转多家医院治疗效果不佳，最终确诊为类风湿肺结节，经托珠单抗联合激素及来氟米特治疗后病情改善。通过分析该病例的临床特点及诊治经过，并复习相关文献，提高临床医生对类风湿肺结节的认识。.

Teratogenic agents have been shown to have drastic and detrimental effects on fetuses if exposed to the agent during uterine life. The most sensitive time for a developing fetus is during the first trimester, and teratogenic exposure during this time can lead to severe deformities in the fetus. The Food and Drug Administration has categorized teratogenic agents based on the severity of their effect on the fetus; these categories include A, B, C, D, and X. Category A is the safest, with the most dangerous, and highly contraindicated in pregnant patients being Category X. This review article will discuss the teratogenic agents leflunomide, isotretinoin, thalidomide, warfarin, tetracycline, and angiotensinogen-converting enzyme inhibitors. Leflunomide can cause cranioschisis, exencephaly, and vertebral, head, and limb malformations. Isotretinoin\'s main teratogenic effects include central nervous system malformations, hydrocephalus, eye abnormalities, cardiac septal defects, thymus abnormalities, spontaneous abortions, and external ear abnormalities. Thalidomide has been shown to cause limb deformities, bowel atresia, and heart defects when the embryo is exposed to the agent during development. Warfarin can lead to spontaneous abortion and intrauterine death, as well as nasal hypoplasia, hypoplasia of extremities, cardiac defects, scoliosis, and mental retardation when exposed in utero. Tetracycline\'s teratogenic effects include gastrointestinal distress, esophageal ulceration and strictures, teeth discoloration, hepatotoxicity, and calcifications. Angiotensinogen-converting enzyme inhibitors can cause skull hyperplasia, anuria, hypotension, renal failure, lung hypoplasia, skeletal deformation, oligohydramnios, and fetal death. Teratogenic effects can be avoided if the pregnant patient is educated on the teratogenic effects of these agents.

UNASSIGNED: This study was to assess the safety and effectiveness of immunosuppressive agents, specifically Voclosporin, when used in conjunction with mycophenolate mofetil (MMF) induction therapy for the management of lupus nephritis (LN).
UNASSIGNED: A systematic review and network meta-analysis (NMA) was conducted on randomized controlled trials investigating the efficacy of immunosuppressant-induced therapy for LN. The random effects model was used in the analysis. I2 was used to evaluate the heterogeneity of the model. Odds ratios (OR) and 95% credible intervals (CrI) were computed to assess and compare the relative effectiveness and safety of various treatment protocols.
UNASSIGNED: The study included a total of 16 randomized controlled trials (RCTs) involving 2444 patients with LN. The analysis results indicated that there was no significant difference in terms of partial remission (PR) between the drugs. However, when considering complete remission (CR), the combination of Voclosporin with MMF showed the highest remission rate, followed by Tacrolimus (TAC). Unfortunately, Voclosporin in combination with MMF had the highest risk of infection and serious infection, indicating a lower safety profile.
UNASSIGNED: Voclosporin in combination with MMF demonstrated the highest efficacy as an induction therapy for LN. However, it should be noted that the risk of infection and serious infection was found to be high with this regimen. On the other hand, TAC not only showed efficacy but also had a lower risk of infection and serious infection, making it a favorable option in terms of safety. This study did\' not include results on other adverse events.

The selection of antiviral therapy for BK polyomavirus (BKPyV) infection has been extensively debated. Our study aimed to assess the efficacy and safety of various treatments for BKPyV infection.
We searched PubMed, EMBASE, and Web of Science databases for relevant studies regarding drug treatments for BKPyV viremia/DNAemia published between January 1, 1970 and September 30, 2022. Two independent authors screened the published studies, extracted pertinent data, and evaluated their methodological quality. A meta-analysis was performed using the RevMan software version 4.2.2.
A total of 33 published studies involving 986 patients were included in the meta-analysis. Overall, therapeutic interventions comprised immunosuppression reduction alone or in combination with leflunomide, intravenous immunoglobulin (IVIG), cidofovir, or mTOR inhibitor (mTORi) therapy. The meta-analysis revealed that the efficacy of immunosuppression reduction alone for serum BKPyV clearance was 68% (95% confidence interval [CI]: 0.58-0.77; I2 = 78%). Moreover, the efficacy of immunosuppression reduction in combination with leflunomide, cidofovir, IVIG, or mTORi therapy for serum BKPyV clearance was 61% (95% CI: 0.47-0.74; I2 = 83%), 71% (95% CI: 0.63-0.78; I2 = 0), 87% (95% CI: 0.82-0.93; I2 = 45%), and 80% (95% CI: 0.59-1.00; I2 = 58%), respectively. Compared to immunosuppression reduction alone, immunosuppression reduction combined with IVIG therapy offered a statistically significant benefit in serum BKPyV clearance (P < 0.01) with minimal adverse reactions, whereas other adjunctive drug treatments did not demonstrate considerable effects.
Reducing immunosuppression remains the primary approach for treating BKPyV infection. Although the combination treatment with IVIG proved to be most effective, other agents might offer varied antiviral advantages of high heterogeneity, which should be substantiated in future long-term randomized controlled trials.

We describe a patient with rheumatoid arthritis and Hashimoto\'s thyroiditis who developed chronic diarrhea and subsequently diagnosed with collagenous colitis (CC) 5 years after leflunomide initiation. Cessation of leflunomide resulted in complete resolution of diarrhea within 2 months. Although rare, leflunomide-induced colitis should be considered in patients with otherwise unexplained chronic diarrhea. Diagnosis is challenging as symptom onset can occur many years after leflunomide initiation, but diarrheal symptoms typically resolve within weeks to months of stopping the instigating drug.

Teriflunomide and its prodrug, leflunomide, are disease-modifying medications used to treat relapsing-remitting multiple sclerosis (RRMS) and rheumatoid arthritis (RA), respectively. Peripheral neuropathy is a rare side effect associated with both medications, although the incidence rate and exact pathological mechanism remain unknown. We present a retrospective case series of three patients with RRMS, who developed painful small fiber neuropathy at various timeframes (<6 months, one year, and four years, respectively) while on teriflunomide treatment (14 mg/day); we also engage in a literature review of small and large fiber neuropathy associated with teriflunomide and leflunomide use. All three patients developed small fiber neuropathy following teriflunomide exposure. Laboratory workup was negative for metabolic, infectious, vitamin deficiency-related, and autoimmune etiologies, except for one patient who had chronic metabolic syndromes (impaired glucose, hyperlipidemia) before medication intake. However, the patient developed neuropathy following teriflunomide treatment. Electrophysiological findings were negative for large fiber neuropathy in all three patients with positive skin biopsy, with reduced epidermal nerve fiber density (ENFD) in two of the three patients. Teriflunomide was discontinued in all cases, after which symptoms stabilized. Current literature on leflunomide supports a direct neurotoxic effect or buildup of toxic intermediates from uridine synthesis inhibition. Cessation of teriflunomide use in the described cases resulted in symptom stabilization. Early recognition and treatment may lead to good clinical outcomes in these patients.

Kimura disease (KD) is a chronic inflammatory disorder, which is quite rare and has an unclear and much debated etiology. KD is characterized by painless, nodular, subcutaneous swellings along with lymphadenopathy, encountered in the head and neck region more often. It is also known to affect major salivary glands. It is also associated with elevated Immunoglobulins (IgE) and peripheral blood and tissue eosinophilia. Kimura disease generally affects young Asian males. There is considerable difficulty in arriving at clinical diagnosis and often it is frustrating to both patients and the treating physicians because of the difficulty in its management. We are presenting and reporting a case of Kimura disease in a young adult Indian female patient who presented with a swelling in the left parotid region. We have successfully managed this patient medically with a unique combination of drugs, most of which have already been tried and reported in literature by various authors.

Drug rash with eosinophilia and systemic symptoms syndrome (DRESS syndrome) is a potentially life-threatening, drug-induced, multi-organ system reaction, the most frequently involved organ is liver, followed by the kidneys and lungs.1 Early detection and diagnosis followed by withdrawal of the offending agent is vital to minimise the associated morbidity and mortality. A detailed drug history is vital to identify the causative drugs. Although Spanish guidelines were developed by a panel of allergy specialists from the Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC) and are available in literature from 2020, many clinicians are still unaware about the management of this syndrome. Framing national guidelines for the early diagnosis and Pharmaco-therapeutic management of DRESS will help the healthcare professionals to save the patients from unintended vulnerability. Leflunomide, a drug widely used in rheumatology and orthopaedics must be used with caution since it has the potential to cause DRESS syndrome. We report a case of a lady aged 32 years, presented to our hospital with a history of leflunomide intake and symptoms of DRESS.

The search for new glucocorticoid-sparing disease-modifying anti-rheumatic drugs continues to be an unmet need in large vessel vasculitis (LVV). This report aims to assess the effectiveness and safety of leflunomide (LEF) in Takayasu arteritis (TA) and giant cell arteritis (GCA).
We systematically reviewed the literature, searching for studies evaluating the efficacy of LEF in LVV. A meta-analysis was conducted using the random-effects method.
The literature search identified eight studies that assessed LEF in TAK and seven in GCA. All were uncontrolled observational studies with a high risk of bias, implying a low or very-low certainty of evidence. In TAK, the pooled proportion of patients achieving at least a partial remission was 75% (95% CI: 0.64-0.84), angiographic stabilization was observed in 86% (0.77-0.94) and relapses in 12% (0.05-0.21). The mean reduction in the prednisolone dose (MRPD) after LEF treatment was 15.7 mg/d (10.28-21.16). Adverse events were observed in 8% of patients (0.02-0.16). Comparison of LEF with methotrexate (MTX) or cyclophosphamide revealed LEF to be superior in terms of remission induction, relapse prevention, and tolerance. When compared with tofacitinib, both drugs demonstrated comparable efficacy. In GCA, the pooled proportion of patients achieving at least a partial remission was 60% (0.17-0.95). The MRPD after LEF treatment was 15.63 mg/d (1.29-32.55) and 53% of the patients were able to discontinue glucocorticoids (0.25 - 0.80). Relapses were observed in 21% of cases (0.14- 0.28) and adverse events in 28% (0.12-0.46). Comparison of LEF with MTX showed similar efficacy and tolerance.
LEF is well tolerated and might be effective for patients with TAK and GCA.