Acute Kidney Injury in Systemic Sclerosis Beyond Scleroderma Renal Crisis: A Case-Control Study.

BACKGROUND AND OBJECTIVES: Renal involvement in systemic sclerosis remains a significant concern with the focus often centered on scleroderma renal crisis (SRC). However, the broader spectrum of renal manifestations, beyond SRC, remains underrecognized. In our case-control analysis, we describe other causes, risk factors, and renal outcomes of acute kidney injury (AKI) in systemic sclerosis other than SRC. METHODS: Patients diagnosed with SSC, with and without AKI, between 2017 and 2023 at Albany Medical Center, were included in the case-control study using International Classification of Diseases, 10th Revision codes and electronic medical records. Patients with SRC were carefully excluded. Data were collected and compared between AKI and non-AKI groups for patients' demographics, clinical characteristics, and baseline treatment. Additionally, data were collected for baseline, peak, and follow-up creatinine, etiology of AKI, treatment, and outcomes. Statistical analysis was performed using R (version 4.3.0) and Minitab (V19). Categorical variables were presented as frequencies/percentages, and continuous variables as means/standard deviations. Associations between categorical variables were assessed by χ2 test and Fisher exact test. Odds ratios and 95% confidence intervals were calculated using binary logistic regression to separately assess the effect of each independent variable on the odds of AKI. Statistical significance was set at p < 0.05. RESULTS: A total of 74 cases were identified. Out of these 74 cases, 27 had AKI and 47 did not have AKI. Out of the 27 AKI cases, 4 with SRC were excluded. Advanced age, chronic kidney disease, and heart failure were identified as risk factors for AKI development. The predominant cause of AKI was prerenal etiology, accounting for 47.8% (n = 11) of cases. This was followed by cardiorenal syndrome and acute tubular necrosis, accounting for 21.7% and 17.3% of the cases, respectively. Most of the cases with AKI had complete renal recovery 78% (n = 18), whereas 17% (n = 4) had progression of the underlying chronic kidney disease. One patient progressed to end-stage renal disease requiring hemodialysis. CONCLUSIONS: This analysis highlights the risk factors and variable clinicopathological courses of renal involvement in patients with scleroderma. This may range from mild AKI with good prognosis to life-threatening SRC.

Spectrum of renal disease in scleroderma other than scleroderma renal crisis: A review of the literature.

BACKGROUND: Systemic sclerosis (SSc) is a multi-system rheumatic disease characterized by vascular and fibrotic manifestations that can affect practically every organ. Scleroderma renal crisis (SRC) is the most common renal manifestation of SSc. However, with the use of angiotensin-converting enzyme inhibitors (ACEi), the morbidity and mortality associated with SRC has significantly reduced. Renal manifestations in SSc other than SRC have been generally under-recognized and can be left untreated, which can lead to grave consequences in this patient population. In this article, we will describe the spectrum of renal disease in SSc besides SRC. MATERIALS AND METHODS: A literature search was conducted on PubMed and Cochrane from inception to December 2022 using medical subject headings (MeSH) terms for "scleroderma", "systemic sclerosis" combined with "renal injury", and "renal dysfunction". We included case reports, case series, observational studies, and literature reviews. RESULTS: The initial search revealed 393 articles. After the exclusion of duplicates and non-relevant articles, data was included from 30 articles and 45 patients. The mean age was 55.2 years, 9 males (20%) and 36 females (80%). The most reported renal manifestations included: ANCA-associated vasculitis (n = 22), penicillamine-induced renal injury (n = 8), oxalate nephropathy (n = 5), Goodpasture syndrome (n = 4), nephrotic range proteinuria (n = 2), renal artery stenosis (n = 2), membranous glomerulonephritis (n = 1), and Evans syndrome (n = 1). CONCLUSION: The spectrum of kidney involvement in SSc can range from asymptomatic reduction of the glomerular filtration rate to life-threatening scleroderma renal crisis. Therefore, it is essential that physicians closely monitor renal function in these patients for any emerging renal dysfunction.

Significant CA 19-9 elevation in IgG4-related autoimmune pancreatitis - A diagnostic dilemma.

IgG4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder characterized by dense infiltration of IgG4-positive plasma cells in the affected tissue along with characteristic storiform fibrosis that can lead to the development of tumefactive lesions in any organ. CA19-9 is a marker for pancreato-biliary malignancy, however mild to moderate elevation of CA 19-9 can also be observed in IgG4-RD autoimmune pancreatitis (AIP) and sclerosing cholangitis (IgG4-SC). Therefore, it becomes difficult to differentiate between these entities. We describe the case of a 65-year-old male with history of IgG4-RD, presenting with jaundice and abdominal pain. He was found to have a pancreatic mass with significantly elevated IgG4 162 (2-96 mg/dL and CA19-9 levels 2830 (0-35 U/ml). Patient underwent ERCP and biopsy, which ruled out pancreatic cancer and cholangiocarcinoma. He was diagnosed with IgG4-RD autoimmune pancreatitis (AIP) and sclerosing cholangitis. Treatment with steroids and rituximab resulted in significant improvement in the bilirubin and a dramatic decrease in CA19-9 levels.

Studying the Role of C5-Inhibition Therapy in Scleroderma Renal Crisis-Induced Thrombotic Microangiopathy - A Review of Literature.

BACKGROUND: The pathogenesis of scleroderma renal crisis (SRC) remains poorly understood but a growing body of evidence suggests that activation of the complement system may be involved in the disease. Recent studies have shown that Eculizumab (monoclonal antibody directed against the complement component C5) is effective in treating patients with SRC who present with symptoms of thrombotic microangiopathy (SRC-TMA). OBJECTIVES: In this study, we conducted a systematic review to characterize the published experience of the presentation and outcome of patients with SRC who were treated with C5 inhibitor, Eculizumab. METHODS: A literature search was conducted from inception to December 2022 using Medical Subject Headings (MeSH) terms for 'scleroderma', 'scleroderma renal crisis, and 'Eculizumab'. We included case reports, case series, and observational studies which reported the use of Eculizumab with or without Angiotensin-converting enzyme inhibitors (ACE-I) for the treatment of scleroderma renal crisis (SRC) in patients with systemic sclerosis. RESULTS: The study included 17 patients, all of whom were treated with Eculizumab. Additionally, the use of ACE-I was reported in 11/17 (64.7%) patients. Further, plasmapheresis was used in 9/17 (52.9%), steroids in 5/17 (29.4%), cyclophosphamide in 3/17 (17.6%), calcium channel blockers in 3/17 (17.6%), and Rituximab in 3/17 (17.6%) patients. Renal replacement therapy was required in 11/17 (64.7%) patients. 14/17 patients (82.3%) were reported to have clinical (renal or hematologic) improvement with Eculizumab therapy (Table 1). CONCLUSION: These findings should prompt testing on a larger cohort of SRC-TMA patients. This would help us determine whether aggressive treatment combining ACE-I and Eculizumab can target the various underlying endothelial, inflammatory, and immunologic mechanisms involved in SRC-TMA, and improve patient outcomes.

Familial Association of Granulomatosis With Polyangiitis: A Case-Based Review of Literature.

Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a class of small vessel vasculitis that includes granulomatosis with polyangiitis (GPA), eosinophilic GPA (EGPA), and microscopic polyangiitis (MPA). Despite extensive research, the mechanisms behind AAV etiology remain obscure. The genetics of AAV is a complex area of investigation because of the rarity of familial cases. However, recent multi-center genome-wide association studies (GWAS) have greatly contributed to our understanding of the genetic basis of AAV. In this study, we report a rare occurrence of GPA in two Caucasian family members who presented with similar clinical symptoms and performed a comprehensive review to study the present literature available regarding the heritability of this disease.

Cardiac Manifestations of Sjogren's Syndrome: A Review of Literature.

Sjogren's syndrome (SS) is a chronic inflammatory disorder of the exocrine glands. It is characterized by a lymphocytic infiltrate in the lacrimal and salivary glands causing keratoconjunctivitis sicca and xerostomia. Extra-glandular involvement may be present in about one-third of patients with primary Sjogren's syndrome (pSS). The most commonly affected organs are the thyroid, lungs, gastrointestinal tract, kidneys, skin, and nervous system. Cardiac manifestations of Sjogren's syndrome are rare and not well-described in the current literature. Most of the evidence is present in the form of case reports and small case series. However, recent studies have shown that patients with Sjogren's syndrome (SS) seem to have a greater overall risk of cardiovascular (CV) events. Although not conventionally considered a feature of the disease, cardiac manifestations can lead to increased morbidity and mortality in this patient population. In this review article, we study the association between cardiac diseases and primary Sjogren's syndrome.

Systemic Haemophilus parainfluenzae Infection Manifesting With Endocarditis and Membranoproliferative Glomerulonephritis.

Infective endocarditis (IE) is a potentially fatal disease that is primarily caused by Staphylococci and Streptococci. The HACEK group of bacteria (Hemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae) account for only 1-3% of reported IE cases. IE has long been known to cause glomerulonephritis. The most common histologic patterns seen are crescentic and diffuse proliferative glomerulonephritis. Notably, membranoproliferative glomerulonephritis (MPGN) is one of the less common patterns seen with IE. We present a rare case of MPGN associated with Haemophilus parainfluenzae endocarditis. A 56-year-old male with no significant past medical history presented to a local hospital with complaints of fever, night sweats, dyspnea, diarrhea, and dark urine for about a month. He was found to have a hemoglobin of 4g/dL, requiring multiple transfusions. He also had bilateral pleural effusions and pulmonary edema. In the following days, he had worsening renal function and was transferred to our hospital for further workup. Initial labs showed anemia, thrombocytopenia, and leukocytosis. He had creatinine elevated at 5.28 mg/dL and a low estimated glomerular filtration rate (eGFR) of 12 mL/min/1.73m2. Urinalysis showed proteinuria, urine hemoglobin, urine white blood cells (WBCs), and red blood cells (RBCs). Blood cultures revealed H. parainfluenzae. Transesophageal echocardiogram (TEE) showed large vegetations with perforation of the mitral valve leaflet. Serology showed low complement levels. Renal biopsy displayed a membranoproliferative pattern of glomerulonephritis on light microscopy. The hepatitis panel was negative, as was the autoimmune workup. The patient was diagnosed with MPGN associated with H. parainfluenzae endocarditis. His complex clinical course required mitral valve replacement and aortic valve repair. He completed the course of antibiotics, with improvement in renal and cardiac function.

Diffuse alveolar hemorrhage: Rare presentation of type 1 cryoglobulinemia in marginal B-cell lymphoma.

Cryoglobulinemia (CG) is defined as the presence of abnormal immunoglobulins (Igs)that precipitate at low temperatures and dissolve upon warming. The manifestations in type I cryoglobulinemia are often related to intravascular obstruction which include skin, joint, renal and neurological involvement. We report a rare case of type 1 CG that presented with diffuse alveolar hemorrhage. Following extensive workup, the patient was found to have membranoproliferative glomerulonephritis secondary to type 1 CG in the setting of marginal B cell lymphoma. He was started on an aggressive regimen targeting underlying lymphoma. Key to managing this condition was multidisciplinary approach towards the diagnosis and management of this otherwise challenging case.

Case of idiopathic multicentric Castleman's disease: the master mimicker.

A woman in her 20s with no medical history presented with progressive abdominal distension, right-sided abdominal discomfort, fatigue and nausea. Examination showed multifocal lymphadenopathy and hepatomegaly with tense ascites. Investigations revealed a multisystem inflammatory condition characterised by elevated acute phase reactants, anaemia, thrombocytopenia, acute kidney injury, lymphocytic ascites, hypoalbuminaemia and hypergammaglobulinaemia. HIV and human herpes virus-8 tests were both negative. In the presence of elevated ANA and SS-A/Ro antibodies, the patient was suspected to be carrying a connective tissue disease, most likely systemic lupus erythematosus (SLE). Clinical and laboratory findings fulfilled the diagnostic criteria for SLE. However, lymph node biopsy showed interfollicular plasmacytosis, associated with high interleukin 6 (IL-6) and vascular endothelial growth factor titers, together hinting towards a rare diagnosis of multicentric Castleman's disease (MCD). As we investigated further, renal biopsy was consistent with thrombotic microangiopathy which has been previously reported in MCD. Furthermore, immune staining on the renal biopsy was negative for 'full-house' immunoglobulin and complement staining pattern, which is specific for lupus nephritis, helping us exclude SLE. In light of these new findings, the patient was started on anti-IL-6 therapy which provided a successful outcome.

A Case of Mixed Type II Cryoglobulinemic Vasculitis Associated With Marginal Zone B-cell Lymphoma.

Our patient is a male in his 40s with a past medical history of sickle cell trait, factor V Leiden mutation, marginal zone B-cell lymphoma, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and sarcoidosis who presented with the complaint of hemoptysis, dyspnea, abdominal pain, arthralgias, peripheral edema of the lower extremities with petechial rash, and oliguria. Investigations revealed acute kidney injury and bilateral transudative pleural effusion. Serology was positive for elevated rheumatoid factor, low complement components, and cryoglobulins. Renal biopsy showed membranoproliferative cryoglobulinemic glomerulonephritis with deposition of monoclonal IgM and IgG3 with kappa light chain and C3 component. The patient was diagnosed with mixed type II cryoglobulinemic vasculitis in the setting of untreated marginal B-cell lymphoma. He had a complex clinical course, requiring multiple intubations, hemodialysis, and treatment with intravenous immunoglobulin, plasmapheresis, steroids, and chemotherapy, to which he initially responded. During treatment, he developed cardiomyopathy associated with congestive heart failure and passed away due to cardiac arrest. We present a rare case of mixed type II cryoglobulinemic vasculitis secondary to untreated marginal zone B-cell lymphoma in a hepatitis C virus (HCV) negative patient, which has not been reported before.

Rapid Resolution of Post-COVID-19 Inflammatory Syndrome in an Adult With Targeted Inhibition of Interleukin-1B.

Multisystem inflammatory syndrome (MIS) is a severe inflammatory response that occurs days to weeks following the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19). Initially known in children and named MIS-C, recently several cases of MIS in adults have been reported to the Centers for Disease Control and Prevention (CDC), leading to the recognition of a new disease MIS in adults (MIS-A). The current treatment options include high-dose steroids, intravenous immunoglobulin (IVIG), and immunosuppressive therapy. However, the pharmacologic approach remains limited to case reports and pending official guidelines to treat cases with MIS-A.  We present a case of an adult patient who had a severe inflammatory state following COVID-19 infection, who was treated with IL-1 antagonist therapy with a successful outcome.

How strong is the evidence that it is possible to get SARS-CoV-2 twice? A systematic review.

With a large number of coronavirus disease 2019 (Covid-19) patients being discharged from hospital with negative test results for SARS-CoV-2, it has been reported that several recovered cases tested positive after discharge (re-positive, RP). This finding has raised several important questions for this novel coronavirus and Covid-19 disease. In this review, we have discussed several important questions, including: (1) Can the virus re-infect recovered individuals? (2) What are the possible causes of the re-positive reverse transcriptase-polymerase chain reaction (RT-PCR) test in recovered patients? (3) What are the implications of these re-positive cases concerning the spread of the virus? Understanding how recovery from Covid-19 confers immunity to decrease the risk of re-infection is needed to inform current efforts to safely scale back population-based interventions, such as physical distancing. We have also described what is currently known about the immune response to Covid-19, highlighted key gaps in knowledge, and identified opportunities for future research. Overall, the quality of the evidence is poor and we describe the features that should be described for future cases.

Pharmacological Primary Prevention of Diabetes Mellitus Type II: A Narrative Review.

The evolving epidemic of type 2 diabetes mellitus has challenged health-care professionals. It stands among the leading causes of mortality in the present world. It warrants new and versatile approaches to improve mortality and the associated huge quality-adjusted life years lost to it once diagnosed. A possible venue to lower the incidence is to assess the safety and efficacy of various diabetes prevention strategies. Diet and exercise have a well-developed role in the prevention of weight gain and, ultimately, diabetes mellitus type II in high-risk individuals. However, high-risk individuals can also benefit from adjunct pharmacotherapy. In light of this information, we decided to conduct a systematic review of randomized controlled trials. This article summarizes the evidence in the literature on the pharmacological prevention of diabetes in high-risk individuals.