Spectrum of renal vascular lesions among patients with lupus nephritis: An experience from a tertiary care center.

Background: Lupus nephritis (LN) is the assemblage of glomerular, tubulointerstitial and vascular changes. Despite the fact that glomerular changes are overemphasized in pathological classification and scoring system, but the existence of vascular damage negatively impact the clinical course. Aims and Objective: This study was conducted to determine the clinicopathological spectrum of renal vascular lesions in lupus nephritis. Materials and Methods: Renal microvascular lesions in biopsy proven lupus nephritis were classified into 5 major categories-thrombotic microangiopathy, true vasculitis; lupus vasculopathy, uncomplicated vascular immune deposits, and arterial. Clinical details, laboratory parameters and histopathological variables were compared among all groups. Summary of chronic changes was also assessed. Results: Biopsies from 56 patients revealed thrombotic microangiopathy (2), lupus vasculopathy (3), uncomplicated vascular immune deposit (6), PAN type vasculitis (1) and arterial sclerosis (13). No renal vascular lesions were found in 35.18% of patients. At the time of biopsy, arterial sclerosis or lupus vasculopathy patients were older Nephritis subtype. Activity indices were higher in lupus vasculopathy group whereas patients with arteriosclerosis showed highest chronicity index. Conclusions: Renal vascular lesions are common in systemic lupus erythematosus patients with nephritis and may be associated with aggressive clinical course.

Utility of serum anti-phospholipase A2 receptor antibody as a biomarker in membranous nephropathy: An experience from a tertiary care center of Eastern India.

Background: Membranous nephropathy (MN) is a pattern of glomerular injury. Exact categorization into primary membranous nephropathy (PMN) or secondary membranous nephropathy (SMN) is essential for treatment. An endogenous podocyte antigen, M-type phospholipase A2 receptor (PLA2R) has been discovered to be involved in the pathogenesis of PMN. Aims and Objectives: In this article, we aimed to analyze renal tissue PLA2R and serum anti-PLA2R antibodies in MN cases and determined the diagnostic utility. Materials and Methods: The study was of prospective type carried out from March 2019 to August 2020. Analysis of cases of MN was performed with PLA2R paraffin immunoflourescence and serum anti-PLA2R antibody ELISA. Results: Overall sensitivity, specificity, PPV, and NPV of serum anti-PLA2R ELISA for PMN was 91.3%, 80%, 75%, and 93.3%, respectively, and of tissue PLA2R staining for PMN was 91.67%, 81.08%, 75.86%, and 93.75%, respectively. There was strong concordance between two methods. In the patients that were followed up, we found baseline serum anti-PLA2R antibody was less in complete remission group than that in non-remission group and the reduction in serum anti-PLA2R antibody was more in complete remission group than that in non-remission group. Conclusion: Routine light and immunofluorescence examination are incapable of giving exact categorical opinion regarding PMN and SMN. Serum anti-PLA2R antibody detection and renal tissue PLA2R analysis are sensitive and specific in detecting PMN. Baseline serum anti-PLA2R antibody and anti-PLA2R antibody quantification trends are related to prognosis of PMN. So they can be incorporated as additional biomarker.

Central Retinal Artery Occlusion in COVID-Associated Mucormycosis.

Introduction: Significant surge of mucormycosis was reported in the Indian Subcontinent during the second wave of the COVID-19 pandemic. COVID-associated mucormycosis (CAM) was defined as the development of features of mucormycosis with prior or current history of COVID-19 infection. Rapid angioinvasion is an important characteristic of mucormycosis. Authors intended to find out the prevalence of retinal arterial occlusion and its association with vascular embolic occlusion elsewhere in the body among CAM patients in this study. Methods: This was an observational study. All consecutive-confirmed cases of mucormycosis (n = 89) and age-/gender-/risk factor-matched controls (n = 324) admitted in the designated COVID center were included in the study. All cases and controls underwent comprehensive ophthalmological, otorhinological, and neurological examinations. All necessary investigations to support the clinical diagnosis were done. Qualitative data were analyzed using the Chi-square test. Quantitative data for comparison of means between the cases and controls were done using unpaired t-test. Results: Twenty-one (23.59%) patients manifested the defined outcome of central retinal artery occlusion (CRAO). Among age-matched control, with similar diabetic status, none had developed the final outcome as defined (P < 0.05). About 90.47% of subjects with CRAO presented with no perception of light vision. Thirteen subjects (61.9%) with the final outcome developed clinical manifestations of stroke during the course of their illness with radiological evidence of watershed infarction (P = 0.001). Orbital debridement was performed in 9 (42.85%) subjects while orbital exenteration was done in 8 (38.09%) subjects. Conclusions: CRAO in CAM patients was found to have aggressive nature turning the eye blind in a very short period of time. CRAO can serve as a harbinger for subsequent development of more debilitating and life-threatening conditions such as stroke among CAM patients.

Cutaneous Vesiculobullous Lesions: A Clinicopathologic Study.

Vesiculobullous disorders could be either immunobullous or non-immunobullous. The spectrum was analyzed using histopathology, direct immunofluorescence (DIF), and salt-split technique. Among the 104 patients analyzed, 77 (74%) were immunobullous and 25 (24%) were having non-immunobullous diseases. Bullous pemphigoid (20.2%) is the commonest among immunobullous lesions, and epidermolysis bullosa (11.5%) was the most frequent non-immunobullous lesion. Involvement of the hair and nail and a positive family history were common relationships for non-immunobullous disorders. Immunobullous lesions showed DIF positivity whereas non-immunobullous lesions were DIF negative. Perilesional DIF was more sensitive and specific than lesional DIF. The commonest antibody was immunoglobulin G (IgG) (78.9%) followed by complement 3c (C3c) (38.1%), immunoglobulin A (IgA) (25%), and immunoglobulin M (IgM) (6.6%). No lesion should be considered non-immunobullous unless both lesional and perilesional DIF results were negative.

Clinicopathological Spectrum of Henoch-Schönlein Purpura Vasculitis: An Experience from a Tertiary Care Center.

Henoch-Schönlein purpura (HSP) is a small vessel vasculitis with multiorgan involvement. Renal involvement is the key factor predicting morbidity. We have aimed to analyze the clinicopathological spectrum of HSP vasculitis and HSP nephritis to assess the risk factors associated with kidney involvement. This retrospective study was performed in the department of pathology with collaboration of department of dermatology and department of nephrology of a tertiary care center. All clinical details along with biopsy findings were retrieved. Starting materials of the study were cases of leukocytoclastic vasculitis with only perivascular IgA deposit of more than ++ in the absence of other immunoglobulin and trace complements. To investigate the possible factors that are influential on the development of biopsy-proven HSP nephritis, we divided the whole study population in two groups -group 1: with and group 2: without biopsy-proven nephritis. One-way analysis of variance was carried out during comparative analysis between two groups using IBM SPSS statistics software, version 19 and MedCalc software, version 12.3.0.0. HSP vasculitis comprised 11.6% (n = 19) of total cutaneous vasculitis in 2 years (164 cases) with a mean age of 13.52 ± 8.10 (range: 4-33 years). Three cases developed de novo kidney disease (15.79%). A correlation analysis revealed that predictors were seasonal variation (P = 0.018), severe gastrointestinal involvement (P = 0.03), and subcutaneous edema (P = 0.005). Various clinical and laboratory parameters were associated with renal consequences. Occult nephritis was the most common presentation with crescent as a constant histopathological feature.

Role of light and immunofluorescence microscopy to differentiate primary and secondary membranous nephropathy.

Context: Membranous nephropathy (MN) causes nephrotic syndrome, mostly primary but may be associated with SLE, infections, cancer, or drug. Aims: To estimate clinical, serological, light microscopic, and direct immunofluorescence (DIF) findings to differentiate primary and secondary MN. Settings and Design: Prospective, cross-sectional, single-center study in a tertiary care hospital. Methods and Material: Total 51 cases from September 2019 to February 2020. Laboratory Data: Blood glucose, urine analysis, urea, creatinine, albumin, cholesterol, HBsAg, Anti HCV, ASO, ANA, MPO ANCA, PR3 ANCA, dsDNA, PLA2R, C3, and C4. Clinical parameters: age, sex, BP, skin lesions, arthralgia, edema, obesity. Renal biopsies examined with H and E, PAS, silver methanamine, MT stains. DIF done with IgG, IgM, IgA, C3c, C1q, kappa, and lambda. Statistical Analysis Used: Statistical software (Graph Pad PRISM 6) and Chi-square test). Results: Among 51 cases, 25 are primary and 26 are secondary MN with 22 being lupus nephritis, with 2 being post-infectious and the remaining 2 being proliferative glomerulonephritis with monoclonal immunoglobulin deposition (PGNMIDD) with kappa chain restriction. Mean age was 37 ± 12.18 and 30.69 ± 13.92 years for primary and secondary MN, respectively. Significant male preponderance in primary MN. Serum C4 significantly low in secondary MN (15.34 ± 9.59). Microscopic hematuria present in secondary MN. Mesangial and endocapillary hypercellularity are significant in secondary MN. IgG and kappa are significantly intense in primary whereas IgA, C3c, and C1q are significantly intense in secondary MN. Conclusions: Reliable differentiation between primary and secondary MN has important therapeutic implications.

IgG4 tubulointerstitial nephritis - An uncommon enemy!

IgG4-related disease (IgG4-RD) is an evolving entity characterized by immune mediated multisystem involvement in the form of fibro inflammatory lesions like sclerosing pancreatitis, dacryoadenitis, Reidel thyroiditis, or chronic sclerosing sialadenitis. Barely, the lesions are restricted to kidney (IgG4-RKD: IgG4-related kidney disease) involving either glomerular or extraglomerular compartment. It is challenging to identify and demands an awareness regarding the entity to reduce the number misdiagnosis and missed diagnosis. Here, we report a case of a 45-year-old woman with IgG4 tubulointerstitial nephritis (IgG4-TIN) who presented with unexplained renal dysfunction as her initial manifestation. This is the first case of IgG4-RKD reported from our tertiary care center among 1864 native renal biopsy in the last two years.

Genetic and acquired blistering disorders of pediatric age group: An experience from Eastern India.

INTRODUCTION: Blistering or vesiculobullous disorders in pediatric population are either immunobullous or mechanobullous. Spectrum was analyzed using demographic details, clinical features, histopathology, direct immunofluorescence (DIF) and Immunofluorescence mapping (IFM). METHODOLOGY: This was a single institution based observational study in children below 18 years. The demographic details were collected using proforma containing particulars of the patient, history, complaints, and other parameters. Punch biopsy of the skin lesion was done. Biopsy samples were examined under light microscope followed by DIF using fluorescent conjugated polyclonal antibody against immunoglobulins IgG, IgM, IgA, and complement C3. The salt-split technique was also used in particular cases. IFM was done using anticytokeratin (CK) 5 & 14, antilaminin 332, anticollagen VII, and anticollagen IV antibodies. RESULTS: Out of total 50 cases, linear IgA bullous dermatosis (LABD) was the commonest. The average concordance between clinical and final diagnosis (histopathological examination + DIF) was 87.5% and discordance was 12.5%. The agreement between histopathological examination and DIF was found to be substantially significant (κ = 0.6892). IFM depicted epidermolysis bullosa simplex with reduced CK 14 expression, dystrophic epidermolysis bullosa with reduced Collagen VII expression and junctional epidermolysis bullosa with absent laminin 5 expression. CONCLUSION: The spectrum of bullous lesions in childhood was properly delineated and subcategorization of EB was done. Histopathological examination showed the hallmarks that were conclusive in most of the cases except in LABD and EB. DIF and IFM proved indispensable in those cases. Thus, DIF is not a substitute for histopathology but complementary to it.

A tale of monoclonal immunoglobulin: Clinicopathological analysis of proliferative glomerulonephritis with monoclonal immunoglobulin deposit.

BACKGROUND: Proliferative glomerulonephritis with monoclonal immunoglobulin deposit (PGNMID) is an entity with a variable clinical and histological spectrum, which mimics immune-complex mediated glomerulonephritis on light microscopy. In this article, we aim to describe the clinical and pathological features of six cases of PGNMID that we encountered during our routine practice. MATERIALS AND METHODS: The study was of the prospective type carried out from February 2018 to August 2019. The renal biopsies that we received in our department, were processed for light microscopy, immunofluorescence microscopy, and electron microscopy. Light microscopic findings were carefully re-evaluated by two experienced renal pathologists. Key diagnostic features were 1) Monoclonal staining of glomeruli for one immunoglobulin (Ig) subclass and single light chain, 2) Membranoproliferative glomerulonephritis (MPGN) pattern (rarely membranous or crescentic), 3) Subendothelial and mesangial (rarely subepithelial) deposits. RESULTS: : We diagnosed five cases of IgG PGNMID and one case of IgA PGNMID with a mean age 53 ± 10.33 years. The most common histological pattern, seen in three cases was MPGN. IgG3 deposits were identified in five cases out of which k light chain restriction was present in four cases and λ light chain restriction was present in one case. IgA deposits were identified in one case that had λ light chain restriction. One patient suffered from multiple myeloma. CONCLUSIONS: The renal biopsy especially immunofluorescence analysis is the key modality for diagnosis of PGNMID where it shows staining of the glomerulus for a single heavy-chain subclass and a single light-chain isotype. Electron microscopic evaluation is necessary to differentiate PGNMID from other renal diseases with monoclonal immunoglobulin deposits.

A tale of tripartite: An experience from a tertiary care center of Eastern India.

BACKGROUND: Crescentic glomerulonephritis (Cr GN) is pattern of glomerular injury resulting from wide range of diseases sharing a common pathogenesis. OBJECTIVES: The objective of our study was to analyze the clinicopathological spectrum and outcome of Cr GN with special reference to its immunopathological subtypes using a panel of immunofluorescence stains. MATERIALS AND METHODS: Native renal biopsies with crescentic pattern of injury were included. Detailed Clinical and laboratory variables were analyzed along with the treatment protocol and renal outcome, wherever available. Renal biopsy slides were evaluated for various glomerular and extraglomerular features. Both qualitative and quantitative data were analyzed. RESULTS: A total of 57 cases of Cr GN were included; majority (47.36%) of cases were pauci-immune in nature. Among clinical features, ranges of proteinuria and creatinine level were significantly different between subgroups. The various light microscopic parameters, including proportion of cellular crescents and capillary wall necrosis were different. Presence of arteriolar changes also showed association with unfavorable outcome. Three unusual associations, including IgA nephropathy, membranous glomerulonephritis and Hepatitis B infection were detected. Adequate follow-up information was available in 35 of the patients. Of these, 14 were dialysis-dependent at the last follow-up. CONCLUSIONS: Type III Cr GN (pauci-immune Cr GN) was the commonest cause of Cr GN in our population. Adult patients required renal replacement therapy more frequently than pediatric cases those are chiefly infection associated. Critical appraisal of clinical, histopathological and immunofluorescence finding help to identify individual subtypes as treatment and outcome varies accordingly.

COVID-19 associated rhino-orbital-cerebral mucormycosis: An observational study from Eastern India, with special emphasis on neurological spectrum.

AIMS: 1: Describe the epidemiology and determine risk factors for COVID-19 associated mucormycosis. 2: Elaborate the clinical spectrum of Rhino-Orbital-Cerebral Mucormycosis (ROCM), pattern of neuroaxis involvement and it's radiological correlates. METHODS: Observational study. Consecutive, confirmed cases of mucormycosis (N = 55) were included. A case of mucormycosis was defined as one who had clinical and radiological features consistent with mucormycosis along with demonstration of the fungus in tissue via KOH mount/culture/histopathological examination (HPE). Data pertaining to epidemiology, risk factors, clinico-radiological features were analysed using percentage of total cases. RESULTS: Middle aged, diabetic males with recent COVID-19 infection were most affected. New onset upper jaw toothache was a striking observation in several cases. Among neurological manifestations headache, proptosis, vision loss, extraocular movement restriction; cavernous sinus, meningeal and parenchymal involvement were common. Stroke in ROCM followed a definitive pattern with watershed infarction. CONCLUSIONS: New onset upper jaw toothache and loosening of teeth should prompt an immediate search for mucormycosis in backdrop of diabetic patients with recent COVID-19 disease, aiding earlier diagnosis and treatment initiation. Neuroaxis involvement was characterized by a multitude of features pertaining to involvement of optic nerve, extraocular muscles, meninges, brain parenchyma and internal carotid artery.

Pediatric lupus nephritis - An evil cousin of its adult counterpart: A single-center based experience from a tertiary care hospital of Eastern India.

CONTEXT: Systemic lupus erythematosus is an autoimmune multisystem disease with a high predilection for renal involvement. Lupus nephritis develops in 20% to 75% within the first two years. Presentation varies from subnephrotic proteinuria to end-stage renal disease. AIMS: To study clinical features, biochemical, and serological parameters and correlate with histological activity and chronicity score [modified National Institute of Health (NIH) score]. SETTINGS AND DESIGN: Retrospective, cross-sectional, single-center based study in a tertiary care hospital of Eastern India. SUBJECTS AND METHODS: We incuded 36 children with lupus nephritis diagnosed from February 2018 to March 2019. Laboratory data included were complete blood count (CBC), blood glucose, urine analysis, serum urea, creatinine, blood urea nitrogen (BUN), albumin, cholesterol, HBsAg, antihepatitis C virus (HCV) antibody, antistreptolysin O (ASO) titer, antinuclear antibody (ANA), myeloperoxidase antineutrophil cytoplasmic antibody (MPO ANCA), proteinase 3 antineutrophil cytoplasmic antibody (PR3 ANCA), double-stranded DNA (dsDNA), C3, and C4. Clinical parameters were age, sex, blood pressure (BP), skin lesions, arthralgia, edema, obesity. Renal biopsies examined with light microscopy, hematoxylin and eosin (H and E), periodic acid-Schiff (PAS), silver methanamine, Masson's trichrome (MT) stains. Immunofluorescence microscopy done with IgG, IgM, IgA, C3c, C1q, kappa, lambda antibodies. STATISTICAL ANALYSIS USED: Kruskal-Wallis and χ2 tests. RESULTS: Mean age was 15.12 ± 3.49 and 12.5 ± 1.73 years for lupus nephritis (LN) with activity and LN without activity, respectively. Mean dsDNA was higher and mean C3 was lower (52.35 ± 22.21 mg/dl) in active LN. Mean 24-hour urinary protein was higher in LN without activity. Serum creatinine was raised in active LN. LN class III and IV showed higher activity than chronicity. CONCLUSIONS: Pediatric LN is proliferative and more active as compared with adult counterparts. Activity scores are much higher than chronicity scores.