An Unusual Cause of Fever, Bilateral Ear Discharge, Lung Nodules, and Polyuria in a Young Male Post Coronavirus Disease 19.

We present a case of a young male with pyrexia of unknown origin, bilateral ear discharge, lung nodules and polyuria within four weeks of recovering from a moderate Coronavirus disease-19 infection. To the best of our knowledge, this is the first case of post- Coronavirus disease-19 Granulomatosis with Polyangiitis with overlapping large vessel vasculitis with a favorable outcome.

Oxcarbazepine-induced toxic epidermal necrolysis in lupus erythematosus: Turning into a "frequent" rarity but is it diagnosing that matters?

Classic Toxic Epidermal Necrolysis (TEN) in Lupus Erythematosus (LE) is rare and that caused by oxcarbazepine is even rarer. It can be triggered/induced by various insults, the most prominent being drugs. Herein, we describe a young female, a diagnosed case of LE with lupus nephritis, with recent-onset central nervous system vasculitis (incidentally detected on neuroimaging while she was being evaluated for a recent-onset behavioural change), who within a month of exposure to the drug developed an extensive exfoliating skin rash with mucosal lesions, which on histopathological evaluation showed TEN in LE, triggered by Oxcarbazepine, which was commenced for seizure prophylaxis. She was managed with pulse methylprednisolone, followed by intravenous immunoglobulin (IVIg), after which she made a satisfactory recovery. It is highlighted that TEN in LE patterns must be recognized in an emergency and Acute Syndrome of Apoptotic Panepidermolysis (ASAP) concept applied promptly without awaiting diagnoses. Further, many common drugs possibly trigger this pathology making the rara-avis not rare anymore!

Fever of Unknown Origin and Hepatitis as the Initial Presentation of Anti-MDA-5 Positive Dermatomyositis: A Case Report.

Petersdorf and Beeson first defined fever of unknown origin (FUO) in 1961, and subsequently, over the next 60 years, the definition of FUO has changed considerably. In the western world, non-infectious inflammatory diseases are the most common cause of FUO; however, in developing countries, infections remain the leading cause of FUO. Dermatomyositis (DM) is an autoimmune inflammatory disease of unknown aetiology which mainly affects skin and muscles. Anti-melanoma differentiation-associated protein 5 (MDA-5) positive DM generally presents with classical cutaneous manifestations, early interstitial lung disease, and patients generally do not have clinical features of muscle involvement. We present a case of a 39-year-old male who presented with FUO and hepatitis and was diagnosed as clinically amyopathic DM after two weeks of admission. Subsequently, he was found to have a high titre of Anti-MDA-5 antibody. This is the first case of Anti-MDA-5 positive DM presenting as FUO and hepatitis with a favourable outcome to the best of our knowledge.

The diagnostic utility of rheumatoid factor and anticitrullinated protein antibody for rheumatoid arthritis in the Indian population.

Background: There is lack of Indian data on diagnostic utility of rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) for diagnosis of rheumatoid arthritis (RA) and prevalence of these antibodies in patients with RA and the healthy population. The study was aimed to assess the diagnostic utility and prevalence of RF and ACPA at different titers in the Indian scenario. Method: All the patients of RA fulfilling the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2010 classification criteria and age and gender-matched healthy controls were included in the study. RF and ACPA were measured by nephelometry and the enzyme-linked immunosorbent assay (ELISA) method, respectively. Result: Of 803 patients (291 men and 512 women) included, the RF was positive in 566 (70.5%) study patients. The ACPA was positive in 527 (71.7%) patients of 735 of them. Among 408 healthy controls, 45 (11%) were RF positive and 19 (4.7%) were ACPA positive.At the positive cutoff level, the RF had a specificity of 87.6% (95% confidence interval [CI] = 84.4-90.8; positive likelihood ratio [LR+] 5.7). Specificity at 2 and 3 times above the upper limit of normal (ULN) increased to 96.2% (95% CI = 94.3-98.1; LR+ 15.7) and 97.1% (95% CI = 95.5-98.7; LR+ 17.1), respectively.The specificity of ACPA at the positive cutoff level was 94.4% (95% CI = 92.2-96.6; LR+ 12.7), which increased to 98% (95% CI = 96.6-99.4), at 2xULN level. The likelihood ratio for ACPA at all cutoff levels measured was more than 10. Conclusion: The sensitivity and specificity of RF and ACPA in our study population are comparable with those of other studies. ACPA at lower titers may have sufficient diagnostic utility for RA in an appropriate clinical setting.

Cases of catastrophic anti-phospholipid syndrome in systemic lupus erythematosus: An experience.

Anti-phospholipid syndrome is an autoimmune disorder characterized by episodes of arterial and/or venous thrombosis and/or pregnancy morbidity in the presence of anti-phospholipid antibodies. Catastrophic anti-phospholipid syndrome is an accelerated form of the disease with rapid involvement of multiple organ systems often posing a diagnostic challenge. There is a paucity of literature on the myriad presentations of catastrophic anti-phospholipid syndrome owing to the orphan nature of the disease. We present three cases of catastrophic anti-phospholipid syndrome in patients with systemic lupus erythematosus that presented with episodes of thrombosis involving both arterial and venous systems and multisystem organ failure. Timely diagnoses were made based on a high index of suspicion and were managed with a combination of systemic glucocorticoids, cyclophosphamide, plasmapheresis, intravenous immunoglobulin and other supportive measures. However, despite providing the standard of care, we encountered a poor outcome in two of these patients, highlighting the high mortality associated with catastrophic anti-phospholipid syndrome.

Serum interleukin-6 in seropositive rheumatoid arthritis and response to tocilizumab: An observational study.

OBJECTIVE: There is no clinically useful biomarker as a predictor of response to any class of biological disease-modifying antirheumatic drugs (bDMARD). Serum interleukin-6 (IL-6) has a major role in the pathogenesis of rheumatoid arthritis (RA) and its serum level in patients of RA may predict response to treatment with IL-6 receptor (IL-6R) antagonist tocilizumab. METHODS: Biological DMARD naïve patients of seropositive RA, fulfilling American College of Rheumatology/European League Against Rheumatism classification criteria 2010, were treated with 06 doses of tocilizumab (8mg/kg) at monthly interval. Baseline and post-treatment serum IL-6 levels were measured and correlated with response to treatment measured by disease activity score-28 joints erythrocyte sedimentation rate (DAS28 ESR) after treatment. RESULTS: The study included 34 patients and 26 (70%) of them achieved DAS-28 remission (DAS28 ESR < 2.6). The baseline serum IL-6 did not correlate with post-treatment DAS28 ESR (R -0.197, P = .264). Though, statistically not significant (P = .085) more patients with comparatively lower baseline serum IL-6 attained DAS28 remission (16 out of 17, P = .085). There was an increase in the serum IL-6 level (median 40.5pg/ml [IQR 130.2] to 72.6pg/ml [IQR 162.5]) after tocilizumab treatment and the change in IL-6 level also did not correlate with post-treatment DAS28 ESR (R -0.240, P = .172). CONCLUSION: Higher number of patients with comparatively lower serum IL-6 level attained DAS28 remission in this study; however, it was not statistically significant. It requires further evaluation in larger studies to make any conclusion on the role of serum IL-6 as a predictor of response to tocilizumab in seropositive RA.

Anti-Jo1 Syndrome: Understanding a Rare Cause of Interstitial Lung Disease.

Background: Anti-Jo1 syndrome is one of the most common amongst the various anti synthetase syndromes (ASS), which forms a subgroup of the idiopathic inflammatory myositis (IIM). It is characterised by myositis, interstitial lung disease (ILD), fever, Raynaud's phenomenon, and mechanic's hands; associated with the presence of anti-Jo1 antibodies in serum. Being an orphan disease, the clinical diagnosis is often delayed. Materials and methods: In this retrospective study, all patients diagnosed as Anti-Jo1 syndrome, from two tertiary care hospitals in Western Maharashtra, between 01 January 2019 - 31 December 2020, were enrolled. The parameters studied included demographic data, clinical features at presentation, laboratory parameters, spirometry, and radiographic findings, along with treatment instituted. Result: A total of 17 patients (8 males, 9 females) qualified for inclusion in the study. The mean age of diagnosis was 40 (±13) years with mean time to diagnosis being 2 years (± 0.6 years), from first clinical presentation. The most common presenting symptoms encountered were arthritis (n = 12, 70.5%), fever (n = 16, 70.5%), myositis (n=11, 64.7%) and breathlessness (n=10, 58.8%).10 patients had ILD at presentation on high resolution computerised tomography of chest (n=10, 58.8%) with restrictive lung defect on spirometry. Six patients required induction of immunosuppression using pulse methylprednisolone (n=6) and Rituximab (n=6), while 11 were managed with oral steroids. Mycophenolate mofetil (n=10) and Azathioprine (n=7) were used as maintenance immunosuppression. Conclusion: Anti-Jo1 syndrome is a myositis syndrome, presenting with a multitude of clinical features. Steroids and disease modifying anti rheumatic drugs form mainstay of therapy.

Synchronous Detection of Extra-Adrenal Paraganglioma in a Follow-Up Case of High-Grade Gastrointestinal Stromal Tumor.

Extraadrenal paragalionoma at multiple sites and its association with GIST is a rare finding. Although 18F-FDG PET-CT is not a modality of choice for primary diagnosis of paraganglioma, and its use is restricted for detection of metastases/multiple sites and disease staging. However, in this case that we describe here, its role in an already-proven/recurrent case of paraganglioma is emphasized by its simultaneous assessment of disease at several different sites.

Pulseless Systemic Lupus Erythematosus: A Rare Presentation.

Vascular disease is frequent in patients with systemic lupus erythematosus, which can be related to the disease process, or can develop as an accompanying co-morbidity and represents the most frequent cause of death in established disease. However, at times the presentations can be uncommon and subtle, and warrants a thorough examination both clinically and radiologically. We report a case of a young female with photosensitive malar rash, oral ulcers, intermittent fever with joint pains, history of two abortions, and unilateral absent radial and brachial artery pulses on clinical examination. The evaluation revealed positive antinuclear antibody (4+), anti-Smith antibody (2+), direct Coomb's test (2+), and antiphospholipid antibody panel was negative. Color doppler flow imaging of right upper limb (arterial) revealed irregular wall thickening with a narrow lumen and mildly reduced peak systolic volume. Computed tomography aortogram revealed wall thickening and luminal narrowing involving the entire length of the right brachial and radial artery. We report this case for its rarity and unique presentation of medium vessel vasculopathy.

Clinico-etiological characteristics of organizing pneumonia: A retrospective study.

INTRODUCTION: Organizing pneumonia (OP) is an idiopathic interstitial pneumonia characterized radiologically by the patchy peripheral areas of ground-glass opacities and consolidation. It is commonly associated with a variety of conditions such as connective tissue diseases (CTD), drugs, infections, malignancy, radiation exposure, post-transplant, and other interstitial pneumonia. There are no specific clinical manifestations unless there is an underlying etiology. We present a series of such cases. AIMS AND OBJECTIVES: The aim of the study was to identify the clinical characteristics and etiological spectrum of patients manifesting radiologically with OP pattern. MATERIALS AND METHODS: This was a retrospective analysis of clinico-radiological profile and etiological diagnosis of 23 patients, who had a radiological diagnosis of OP during the period of January 2017-September 2019. RESULTS: Our patients presented with nonspecific symptoms of cough, fever, breathlessness, and occasionally with hemoptysis. The various etiologies identified were CTD (n = 4), infection (n = 2), drugs (n = 4), radiation (n = 1), chronic aspiration syndrome (n = 1), malignancy (n = 2), hypersensitivity pneumonitis (n = 1), and chronic heart failure (n = 2), and in majority (n = 7), no underlying etiology was evident and were labeled as cryptogenic organizing pneumonia. CONCLUSION: OP is an underdiagnosed entity and is associated with numerous diseases varying from pulmonary tuberculosis to malignancy. Identification of the underlying disease process is of paramount importance as it enables the treating physician to implement necessary therapeutic interventions.

Cement Factory Worker Presenting With Raynaud Phenomenon, Breathlessness, and Digital Ulcers.

CASE PRESENTATION: A 54-year-old man who had worked in a cement factory for the past 30 years, presented to the chest clinic with complaints of insidious onset, gradually progressive breathlessness with intermittent dry cough of three years' duration. The symptoms were associated with bluish discoloration of fingers on exposure to cold. He also gave a history of digital ulcers at the fingertips of the same duration. These ulcers used to heal, leaving behind pitted scars. There was also an associated history of progressive tightening of skin involving the face, extremities, and trunk. He also complained of food getting stuck in the throat, and he had to take frequent sips of water while eating, along with a feeling of early satiety. There was also a history of skin pruritus. There was no history of arthritis, rash, or alopecia. He had been treated 15 years ago for pulmonary TB, with 9 months of anti-tubercular therapy. He denied any similar illness in the family. On eliciting his occupational history, he revealed that other coworkers in his workspace had complained of a similar illness. He was a nonsmoker and teetotaller with no known addictions or exposure to chemicals.

Diagnostics of Data-Driven Models: Uncertainty Quantification of PM7 Semi-Empirical Quantum Chemical Method.

We report an evaluation of a semi-empirical quantum chemical method PM7 from the perspective of uncertainty quantification. Specifically, we apply Bound-to-Bound Data Collaboration, an uncertainty quantification framework, to characterize (a) variability of PM7 model parameter values consistent with the uncertainty in the training data and (b) uncertainty propagation from the training data to the model predictions. Experimental heats of formation of a homologous series of linear alkanes are used as the property of interest. The training data are chemically accurate, i.e., they have very low uncertainty by the standards of computational chemistry. The analysis does not find evidence of PM7 consistency with the entire data set considered as no single set of parameter values is found that captures the experimental uncertainties of all training data. A set of parameter values for PM7 was able to capture the training data within ±1 kcal/mol, but not to the smaller level of uncertainty in the reported data. Nevertheless, PM7 was found to be consistent for subsets of the training data. In such cases, uncertainty propagation from the chemically accurate training data to the predicted values preserves error within bounds of chemical accuracy if predictions are made for the molecules of comparable size. Otherwise, the error grows linearly with the relative size of the molecules.