Bilateral single system ectopic ureters - A rare variant.

Bilateral single system ectopic ureters are a rare entity in paediatric urology. We report a girl child with bilateral single system ectopic ureters with right system opening into the vagina, who presented at 3.5 years with continuous dribbling of urine & a small capacity bladder. Renal scans and MRI were done which indicated bilateral single system ectopic ureters with hydroureteronephrosis. We managed her surgically by a right nephro-ureterectomy, bladder augmentation, left ureteric reimplantation and Mitrofanoff. Post op patient had acute on chronic renal failure, stabalised by haemodialysis. It is a rare presentation if managed promptly can prevent renal replacement therapy.

A case of bullous systemic lupus erythematosus: Diagnostic challenges and clinical implications.

Skin involvement in systemic lupus erythematosus (SLE) is common. Bullous lesions in SLE patients are usually due to other autoimmune conditions or rarely, due to lupus itself. Bullous SLE is rare blistering disorder characterized by subepidermal blisters. We, hereby, present a case of bullous SLE in a 24-year-old female who responded well to systemic glucocorticoids, mycophenolate mofetil, and dapsone.

Concurrent occurrence of acute pancreatitis and intracerebral hemorrhage as presenting manifestations in lupus: a case report.

Systemic lupus erythematosus (SLE) is a rare autoimmune condition that may affect almost every organ system and has a wide range of disease severity. It is characterized by a spectrum of clinical manifestation, a plethora of autoantibodies, and immune complex formation. The symptoms can come from any organ system, alone or in a group, and they can be of any severity, which makes diagnosis and prognosis difficult. Case presentation: The authors hereby present the case of an 18-year-old female with chief complaints of fever, abdominal pain, headache, vomiting, and loss of vision. She was diagnosed with acute pancreatitis (AP) and intracerebral hemorrhage (ICH) with an etiology linked to SLE. SLICC criterion was used to diagnosed SLE while ATLANTA criteria for AP and neuro-radiological findings for ICH. Emergency temporo- parietal-occipital-osteoplastic craniotomy was done for ICH as well as started with immunosuppressive therapy for SLE. On the 18th day of admission, she was discharge with maintenance medications for SLE. While the vision took over a month to come to a premorbid state, she was clinically improved within 2 weeks of admission. Clinical discussion: Clinical manifestation of SLE vary greatly. AP and intracranial bleeding are few of the rare presentation of SLE. Acute presentation of both conditions in an otherwise healthy individual in the initial course of disease left the clinician with a wide array of differentials. Literature shows very little evidence of co-occurrence of ICH and pancreatitis as an initial manifestation in SLE patients. The exclusive diagnosis of these potentially fatal condition is made holistically with clinical, biochemical, and radiological parameters. Conclusion: SLE may present with atypical, life-threatening initial manifestations. Early diagnosis and timely intervention in therapy can lead to successful management. The treating physician must consider, SLE when a straightforward diagnosis is associated with inexplicable multiple concomitant abnormalities, especially in young women.

Secondary cardiac amyloidosis in a patient with mixed connective tissue disease: A case report.

We report the case of a 62-year-old man who presented with shortness of breath, cough, bilateral lower limbs' swelling, and blackish discoloration of multiple fingertips over the past 2 months. Anti-Ribonucleoprotein antibodies were found to be present, and gadolinium-based cardiac MRI showed non-vascular subendocardial enhancement with diffuse symmetrical thickening of the left ventricular wall. A diagnosis of Mixed connective tissue disease with secondary cardiac amyloidosis was thus made, and the patient was successfully managed with intravenous cyclophosphamide, corticosteroids, and other supportive measures. Although extremely rare, this case shows that secondary cardiac amyloidosis should be considered while managing patients with MCTD.

Case report peripheral ulcerative keratitis with nodular scleritis, presents as the primary manifestation of granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA) is an ANCA-associated autoimmune disorder that typically affects small and/or medium-sized blood vessels. Being a life-threatening disease, with timely suspicion, targeted laboratory investigations, and collaborative management from the ophthalmologist and rheumatologist led to long-term remission of the disease. Case: A 38-year-old female complaining of recurrent deep boring pain with redness in her left eye for many years, which was diagnosed as nodular scleritis with peripheral ulcerative keratitis. The patient also has recurrent bouts of epistaxis and in suspicion of GPA laboratory investigations were carried out and later diagnosed. She was started on cyclophosphamide and is currently under maintenance with rituximab. Case discussion: Ocular involvement has been shown to occur in 20-50% of the population in several studies. It causes conjunctivitis, episcleritis, scleritis, necrotizing keratitis, corneoscleral perforation, posterior uveitis, and optic neuritis. The positive C-ANCA and high PR3 autoantibody have high sensitivity and association with GPA. Cyclophosphamide has been shown to be an effective treatment in multiple studies whereas rituximab has been emerging as a new treatment modality for maintenance, which in turn helps in the remission and relapse of GPA cases. Conclusion: Scleritis and peripheral ulcerative keratitis can be the manifestation of a GPA. Careful evaluation, diagnosis, and management with a multidisciplinary medical team, early start of cyclophosphamide, and rituximab have a huge role in decreasing the disease activity and is life-saving.

Fatal ascending aortic aneurysm in a patient with systemic lupus erythematosus: A case report.

Aortic aneurysm is a potentially life-threatening condition with higher incidence in patients with systemic lupus erythematosus(SLE). Patients usually present with nonspecific symptoms and diagnosis is typically made incidentally through imaging studies. Management strategies include medical therapy to control inflammation and hypertension, surgical intervention for large or symptomatic aneursyms, and close monitoring for early detection of complications. We present a case of a 49-year female with multiple joint pain and other nonspecific symptoms for 7 years. Anti-ds DNA and ANA titre were significantly high and CT angiogram showed ascending aortic aneurysm measuring 5.5 cm. Conservative management was started with steroids, hydroxychloroquine, and antihypertensives, while awaiting surgery. However she suddenly collapsed, probably due to aneurysm rupture and could not be revived. Our case report therefore emphasizes the importance of close surveillance and timely intervention to minimize the morbidity and mortality in these patients.

The pattern of sarcoid uveitis at a tertiary care center in Nepal.

Sarcoidosis is an idiopathic, multisystemic granulomatous disorder involving the eye with various ocular presentations, the most common being sarcoid uveitis. The diagnosis was based on typical clinical features, chest radiography, laboratory findings and biopsy based on revised International Workshop on Ocular Sarcoidosis criteria. Here in, the authors aim to present the first report on the trend of cases of sarcoid uveitis in Nepal. Materials and Methods: A retrospective quantitative cross-sectional study was conducted at the uveitis clinic of the Institute of Medicine by obtaining medical data from the medical record section on sarcoid uveitis cases visiting from March 2018 to March 2021. Demographic profile, ocular findings, laboratory findings and treatment details were documented and statistical analysis was done via Statistical Program for Social Science (SPSS) version 23. Results: Out of 50 eyes of 30 patients included in the study; 66.6% patients (n=20) had bilateral and 33.3% (n=10) had unilateral ocular involvement. Anterior with intermediate uveitis (26.7%) was the most common type of uveitis among the cases. Serum angiotensin converting enzyme was raised in 66.7%, Chest X-ray showed hilar changes in 63.33%, and high-resolution computed tomography showed mediastinal, hilar lymphadenopathy with or without the involvement of the lung in 63.33% of patients. Conclusion: Sarcoid uveitis may have varied ocular presentations, the commonest being anterior and intermediate uveitis. The commonest complications are cataract and cystoid macular oedema, which are associated with vision loss. Steroids and immunomodulators are the mainstays of treatment.

Molecular Insights of MAP4K4 Signaling in Inflammatory and Malignant Diseases.

Mitogen-activated protein kinase (MAPK) cascades are crucial in extracellular signal transduction to cellular responses. The classical three-tiered MAPK cascades include signaling through MAP kinase kinase kinase (MAP3K) that activates a MAP kinase kinase (MAP2K), which in turn induces MAPK activation and downstream cellular responses. The upstream activators of MAP3K are often small guanosine-5'-triphosphate (GTP)-binding proteins, but in some pathways, MAP3K can be activated by another kinase, which is known as a MAP kinase kinase kinase kinase (MAP4K). MAP4K4 is one of the widely studied MAP4K members, known to play a significant role in inflammatory, cardiovascular, and malignant diseases. The MAP4K4 signal transduction plays an essential role in cell proliferation, transformation, invasiveness, adhesiveness, inflammation, stress responses, and cell migration. Overexpression of MAP4K4 is frequently reported in many cancers, including glioblastoma, colon, prostate, and pancreatic cancers. Besides its mainstay pro-survival role in various malignancies, MAP4K4 has been implicated in cancer-associated cachexia. In the present review, we discuss the functional role of MAP4K4 in malignant/non-malignant diseases and cancer-associated cachexia and its possible use in targeted therapy.

A case of oculocutaneous sarcoidosis.

Purpose: To present a case of extrapulmonary sarcoidosis presenting with ocular and cutaneous involvement. Observations: We report a 54-year-male who presented with bilateral redness of eyes, photophobia, and diminished vision for a week. The best corrected visual acuity in the right eye was 6/60 and the left eye was counting fingers close to face (CFCF). He also had multiple brown plaques on the nape of the neck, chest, back, and arms. Furthermore, he was on multiple antipsychotic drugs for schizophrenia for 3 years. Uveitis investigation workup revealed raised serum angiotensin converting enzyme (ACE), negative Mantoux, and other serological tests. The patient was treated for acute anterior uveitis secondary to sarcoidosis. Clinical improvement was seen after a few days following treatment. The patient presented a year later with multiple yellowish conjunctival nodules in the superior bulbar conjunctiva associated with hyperemia. A biopsy of the plaque like skin lesions was done, which suggested cutaneous sarcoidosis. Involvement of the skin and the eyes raised suspicion that the persistent psychotic episodes despite multiple antipsychotic drugs could be attributed to neurosarcoidosis. However, magnetic Resonance Imaging (MRI) of the brain and orbit showed normal findings. After treatment with corticosteroids and immunosuppressives (methotrexate), the conjunctival nodules as well as skin lesions drastically improved, and the psychosis also responded well to clozapine. Conclusion: A high index of suspicion is needed in cases presenting with granulomatous uveitis with multisystem involvement. Long-term follow-up is crucial to monitor the disease progression and adverse effects of medications.

Rise of biologics in noninfectious uveitis: a retrospective cohort study from Nepal.

Uveitis is a sight-threatening disease that poses a heavy burden on the quality of life. The treatment of uveitis has been revolutionized in the past two decades. Most remarkable among these is the emergence of biologics, which have shown to be effective and safer therapeutic option in noninfectious uveitis. Biologics are very useful when conventional immunomodulator therapy has failed or has been poorly tolerated. The most widely used biologics are tumor necrosis factor-α inhibitors (infliximab and adalimumab) with promising results. Other drugs include anti-CD20 inhibitors (rituximab), interleukin-6R-inhibitor (tocilizumab), interleukin-1R-inhibitor (anakinra), and Janus-associated kinase inhibitor (tofacitinib). Methods: A retrospective review of all cases of noninfectious uveitis and scleritis presenting to our center from July 2019 to January 2021 and had been treated with biological therapy were included. Results: We included 12 eyes of 10 patients. The mean age was 42.10±9.71 years. Anterior nongranulomatous uveitis comprised 70% of the cases and the most common etiology of anterior uveitis was spondyloarthritis (seven cases among which five cases were nonradiographic) axial spondyloarthritis (human leukocyte antigen B27 positive) followed by radiographic axial spondyloarthritis (two cases). The first line of treatment in all cases was conventional synthetic disease-modifying antirheumatic agents among which 50% (n=5) had received methotrexate (≥15 mg/week). As a second line of treatment, one or more biologics was used. Majority of the patients received oral tofacitinib 50% (n=5) followed by Inj adalimumab 30% (n=3). One case of Behcet's disease required sequential biologics (Inj adalimumab followed by oral tofacitinib). All patients tolerated and responded well to the treatment and no recurrences were observed after discontinuation of biologics drugs during the follow-up period of 1 year. Conclusion: Biologics are a relatively safe and effective modality of treatment in refractory, recurrent noninfectious uveitis.

Organizing pneumonia as an initial presentation in a male lupus: A rare case report.

Organizing pneumonia (OP) is one of the rare pulmonary manifestations of systemic lupus erythematosus (SLE) which is infrequently reported as a presenting manifestation. Early diagnosis of lupus-related OP with the help of imaging, can drive to prompt initiation of immunosuppressive therapy leading to a better prognosis. We present a case of a 34-year-old young male who presented with fever, myalgia, and a dry cough for 1 month and was later diagnosed as SLE-related organizing pneumonia.

MRI of the brain mimicking autoimmune encephalitis in Sjögren syndrome with chorea: a case report.

Neurologic manifestations in primary Sjögren syndrome (SS) range in prevalence from 8 to 49%, and most of the studies suggest a prevalence of 20%. The incidence of SS patients developing movement disorders is about 2%. Case presentation: The authors herein report a case of a 40-year-old lady with MRI of the brain mimicking autoimmune encephalitis in SS who presented with chorea. Her MRI findings revealed T2 and FLAIR (fluid-attenuated inversion recovery) high signal intensity areas in bilateral middle cerebellar peduncles, dorsal pons, dorsal midbrain, hypothalami, and medial temporal lobes. Clinical discussion: There is still no evidence to support the definite use of MRI in characterizing the central nervous system involvement in primary SS, especially due to overlapping findings with age and cerebrovascular disease. Multiple areas of increased signal intensity in periventricular and subcortical white matter in FLAIR and T2-weighted image is commonly seen in primary SS patients. Conclusion: It is crucial to consider autoimmune diseases like SS as a cause of chorea in adults, even in those whose imaging findings are suggestive of autoimmune encephalitis.

Diminished PD-L1 regulation along with dysregulated T lymphocyte subsets and chemokine in ANCA-associated vasculitis.

ANCA-associated vasculitis (AAV) is a life-threatening disease characterized by small vessel inflammation and pathogenic self-directed antibodies. Programmed death-ligand 1 receptor (PD-1) and programmed cell death ligand-1 (PD-L1) are immune checkpoint molecules crucial for maintaining tolerance and immune homeostasis. After checkpoint inhibition therapy, development of various autoimmune diseases and immune-related adverse events (irAEs) have been observed. Here, we investigated the immunomodulatory roles of neutrophils through the expression of immune checkpoint molecule (PD-L1), migratory molecules (CXCR2), chemotactic chemokines (CXCL5) and other important molecules (BAFF and HMGB1) in development of AAV. We also scrutinized the immune mechanism responsible for development of pauci-immune crescentic GN (PICGN). We demonstrate for the first time that the frequency of PD-L1 expressing neutrophils was significantly reduced in AAV patients compared to healthy controls and correlated negatively with disease severity (BVASv3). Further, in renal biopsy, reduced PD-L1 immune checkpoint expression provides a microenvironment that unleashes uncontrolled activated CD4 + T cells, B cells, neutrophils and macrophages and ultimately causes engulfment of immune complexes leading to PICGN. Furthermore, during remission, reduced neutrophils PD-L1 and CXCR2 expression, increased neutrophils CXCL5 expression and increased peripheral effector memory T cells and increased HMGB1 and BAFF levels in serum, demonstrate the propensity for the persistence of sub-clinical inflammation, which could explain relapse, in this group of diseases.

Scleritis as the harbinger of Granulomatosis with polyangiitis.

Introduction: Ocular and orbital involvement in Granulomatosis with polyangiitis (GPA) is common. GPA can lead to life and sight threatening complications due to necrosis and tissue melting. Cases: We report four cases presenting with ocular pain and redness for varied durations. One had diminution of vision. All of them had deep sectoral/diffuse congestion with one having scleral thinning. All were diagnosed with anterior necrotizing/non-necrotizing scleritis. One had associated penetrating ulcerative keratitis. Topical steroids and systemic non-steroidal anti-inflammatory drugs were started in all cases and rheumatology consultation was taken. Pertinent investigations were sent, and GPA was diagnosed. Intravenous immunosuppressive regimens and oral steroid were started and significant improvements were seen, preventing untoward complications. Conclusion: Scleritis could be manifesting feature of GPA so cautious history taking and evaluation is important. Management often requires multidisciplinary care and ocular features could be the reference guidelines to adjust dose of systemic medications of GPA.

An Unusual Case of Eosinophilia with Systemic Lupus Erythematosus: A Case Report and Review of Literature.

Eosinophilia can be caused by various conditions, parasitic infection being the most common cause. Here, we present a case of a 17-year male who presented with multisystem involvement and eosinophilia. He was later diagnosed to have systemic lupus erythematosus with eosinophilia which is a rare combination. Despite being a diagnostic challenge, these patients can be well managed with immunosuppressive therapy if recognized in time.

Increased gene expression of B cell-activating factor of tumor necrosis factor family, in remitting antineutrophil cytoplasmic antibody-associated vasculitis patients.

AIM: To study the expression of B cell-activating factor of tumor necrosis factor family (BAFF) and A proliferation-inducing ligand (APRIL) genes in active and remitting patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) and healthy controls and their correlation with disease activity. METHODS: This was a prospective case-control study. Gene expressions of BAFF and APRIL were studied in 32 patients with AAV (16 each with active disease and in remission) and 30 healthy age and sex matched controls by real-time polymerase chain reaction. RESULTS: Out of 32 AAV patients, 26 had granulomatosis with polyangiitis (GPA) and 6 had microscopic polyangiitis (MPA). Mean ages of patients in active (12 GPA and 4 MPA) and remission (14 GPA and 2 MPA) groups were 39.4 ± 17.2 and 44.6 ± 16.1 years, respectively. BAFF gene expression was significantly higher in both the active AAV group and remission AAV group compared to controls (P < .01). The BAFF expression was significantly higher in AAV patients in remission compared to active AAV patients (P = .003). In contrast, APRIL expression did not differ between AAV patients and controls (P = .829). However, APRIL had significantly higher expression in remission as compared to active patients (P = .048). There was no significant correlation of both BAFF and APRIL expression with disease activity markers (erythrocyte sedimentation rate, C-reactive protein, platelets and Birmingham Vasculitis Activity Score version 3). CONCLUSION: BAFF gene is significantly expressed in patients with AAV. Among AAV patients, there is a significantly higher expression of BAFF and APRIL in remitting state of the disease as compared to active state. There is no significant change in APRIL gene expression in patients with AAV as compared to controls. This makes a case for anti-BAFF therapy in future for AAV patients in northern India.

Barraquer-Simons syndrome in systemic lupus erythematosus: A case report.

Barraquer-Simons syndrome is a rare entity characterized by progressive loss of subcutaneous tissue in the face and/or upper half of the body and can be associated with autoimmune conditions such as systemic lupus erythematosus. Close long-term follow-up is required to identify metabolic disturbances, potentially life-threatening renal problems, and other associated diseases.

Retroperitoneal Fibrosis as a presentation with masked multiorgan involvement of IgG4-related disease-demystifying the diagnosis: A case report from Nepal.

The timely diagnosis of the disease helps in preventing the progression of RF and unnecessary interventions that may mislead the diagnosis. Biopsy and serum IgG4 both can be non-specific.

Anti-Jo-1 Syndrome Often Misdiagnosed as Rheumatoid Arthritis (for Many Years): A Single-Center Experience.

BACKGROUND: Antisynthetase syndrome is characterized by a triad of myositis, arthritis, and interstitial lung disease. Anti-Jo-1 is the most common associated autoantibody. This study planned to look at the presentation of anti-Jo-1 antisynthetase syndrome in a single Indian center. METHODS AND MATERIALS: This was a medical records review single-center study that included patients with anti-Jo-1 antisynthetase syndrome over 10 years. RESULTS: This study included 27 patients with anti-Jo-1 antisynthetase syndrome, with mean age of 40 ± 9.2 years and female preponderance (female-to-male ratio, 4:1). At presentation, the characteristic triad was present in only 4 patients. A majority presented with the incomplete form, with 2 clinical features (of triad) in 11 and single feature (of triad) being present in 12 patients at initial presentation. Seven presented only with polyarthritis, out of which 6 had been earlier diagnosed as rheumatoid arthritis. Time gap from diagnosis of "rheumatoid arthritis" to antisynthetase syndrome ranged from 3 to 20 years. In patients who had only arthritis in the beginning, there was a significantly longer delay to diagnosis of antisynthetase syndrome, higher frequency of rheumatoid factor, and lower frequency of anti-Ro-52. Overall, outcome was good, with Eastern Cooperative Oncology Group class 1 or 2 in most except 2 patients. CONCLUSIONS: Anti-Jo-1 antisynthetase syndrome commonly presented as incomplete (not a triad) and often only with arthritis. These patients are diagnosed and treated as rheumatoid arthritis for many years, before a diagnosis of antisynthetase syndrome is made. Being aware of this presentation may help in earlier diagnosis by actively searching for subtle clues.

Experience with similar biologic rituximab in 77 patients of granulomatosis with polyangiitis-a real-life experience.

OBJECTIVES: To present single centre experience on the efficacy and safety of similar biologic of rituximab in patients with granulomatosis with polyangiitis (GPA). METHODS: This was a retrospective study of GPA patients who received similar biologic of rituximab as either remission induction or maintenance agent. Demographic parameters, Birmingham Vasculitis Activity Score (BVAS-v3), vasculitis damage index, relapse and adverse events were retrieved from patient records. Outcomes noted were remission at 6 months in remission induction group and rates of relapses, adverse events, serious infections and mortality in both remission induction and maintenance groups. RESULTS: Seventy-seven GPA patients were enrolled. Sixty received rituximab for induction and 57 for maintenance; 69% were anti PR-3 positive. In the induction group, median BVAS-v3 reduced from 12 (IQR 6-21.5) to 0 (0-1) at 6 months. At 6 months, 60% patients attained remission, 40% in primary induction group and 74% in re-induction group (p = 0.016%). In the maintenance group, seven (12%) patients had relapses with median time to relapse of 12 (6-22) months. Median relapse free survival was 21 (6-22) months on rituximab maintenance. There were 12 deaths (15.6%) and 18 serious infections. CONCLUSION: Similar biologic of rituximab was an effective agent for remission induction and remission maintenance in patients with GPA. Head to head trials with innovator molecule are needed to confirm these results. KEY POINTS: • Remission was achieved in 60% of GPA patients who received similar biologic of rituximab as remission induction therapy. • Relapse rate during maintenance phase was 12% with similar biologic of rituximab. Serious infections and mortality with similar biologic of rituximab were comparable with that reported previously in AAV trials.