Background: It has been over a year since the first documented case of the COVID-19 virus was recorded. Since that time, our understanding of this virus has continually evolved, however, its wide-ranging effects are still unfolding. Similar to previously studied viral infections, severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) has been shown to lead to a degree of autoimmunity in patients who are recovering from its effects. Due to its effects on the innate immune system such as the toll-like receptors and complement system, a varying degree of pro-inflammatory markers can become widespread in those who continue to recover from the virus. This case series offers a unique perspective on how COVID-19 has had dramatic effects on those already suffering from inflammatory rheumatic conditions such as rheumatoid arthritis, systemic lupus erythematosus, or fibromyalgia. As the ever-lasting effects of COVID-19 are still unfolding, this case series is one of few to discuss the development and changes of patients with rheumatic conditions. This study hopes to encourage larger studies to be done on the effects of COVID-19 on autoimmune conditions.

Case presentation: Seven patients were identified with new manifestations of rheumatic conditions, which included 3 cases of rheumatoid arthritis, 2 cases of polymyalgia rheumatica, 1 case of reactive arthritis, and 1 case of cutaneous lupus. Post-COVID syndrome was also diagnosed in 7 other patients. Rheumatoid arthritis patients presented with symptoms 4-5 weeks after being diagnosed with COVID-19. Symptoms of polyarticular joint pain, swelling, and morning stiffness were reported in this group. These patients were treated with disease-modifying anti-rheumatic drugs and experienced an improvement of symptoms on follow up. Two cases of Polymyalgia Rheumatica were identified in patients that were previously diagnosed with COVID-19 six weeks prior. One patient had no significant past medical history and the other patient had a history of Rheumatoid Arthritis, which was well controlled. These patients experienced weakness and tenderness in the proximal joints with elevated levels of ESR and CRP. They were treated with prednisone and showed improvement. Reactive Arthritis was diagnosed in 1 patient who presented with swelling in both hands and wrists 1-2 after being diagnosed with COVID-19. This patient began to experience symptoms of Reactive Arthritis 1-2 days after resolution of initial COVID-19 symptoms and this persisted for 3 months. Patient was managed with methylprednisolone injections and NSAIDs, which improved her symptoms. Post-COVID syndrome was identified in 7 patients. All patients were female and had a history of well controlled fibromyalgia. Patients generally experienced fatigue, headaches, and memory fog, which had variable onset from a few days and up to 4 weeks after being diagnosed with COVID-19. One patient had a complete recovery of her symptoms at follow-up 3 months after the initial presentation. The other 6 patients continued to report symptoms of Post-COVID syndrome at follow up. Patients were managed with lifestyle modifications and their previous fibromyalgia treatment.

Conclusion: While cases of COVID-19 continue to rise, complications of this disease are still being discovered. Those who initially recover from COVID-19 may experience new onset rheumatic conditions, worsening of previously diagnosed rheumatic conditions, or Post-COVID Syndrome. As we continue to learn more about the effects of COVID-19, the awareness of these manifestations will play a key role in the appropriate management of these patients.

Keywords: Covid 19; Post Covid; disease flare; post Covid syndrome; reactive arthritis; rheumatoid arthritis; rheumatological manifestation.

Hypersensitivity reactions has been reported with COVID-19 vaccines. Acute eosinophilic pneumonia has not been reported yet after Sinovac/CoronaVac vaccine. A 73-year-old woman presented with maculopapular rash, cough and dyspnea following Sinovac/CoronaVac injection. The complete blood count (CBC) indicated eosinophilia and further evaluation of the eosinophilia with CT and bronchoscopy confirmed a diagnosis of acute eosinophilic pneumonia. After methylprednisolone therapy, her rash resolved with marked improvement of the dyspnea. She is still on treatment and on the follow up period, we plan to continue steroid treatment at least 3 months.

Keywords: COVID-19; COVID-19 vaccines; SARSCoV-2; Sinovac/CoronaVac; eosinophiles; eosinophilic pneumonia; rash.

Background: In a Phase I study treatment with the serum amyloid P component (SAP) depleter miridesap followed by monoclonal antibody to SAP (dezamizumab) showed removal of amyloid from liver, spleen and kidney in patients with systemic amyloidosis. We report results from a Phase 2 study and concurrent immuno-positron emission tomography (PET) study assessing efficacy, pharmacodynamics, pharmacokinetics, safety and cardiac uptake (of dezamizumab) following the same intervention in patients with cardiac amyloidosis.

Methods: Both were uncontrolled open-label studies. After SAP depletion with miridesap, patients received ≤ 6 monthly doses of dezamizumab in the Phase 2 trial (n = 7), ≤ 2 doses of non-radiolabelled dezamizumab plus [⁸⁹Zr]Zr-dezamizumab (total mass dose of 80 mg at session 1 and 500 mg at session 2) in the immuno-PET study (n = 2). Primary endpoints of the Phase 2 study were changed from baseline to follow-up (at 8 weeks) in left ventricular mass (LVM) by cardiac magnetic resonance imaging and safety. Primary endpoint of the immuno-PET study was [⁸⁹Zr]Zr-dezamizumab cardiac uptake assessed via PET.

Results: Dezamizumab produced no appreciable or consistent reduction in LVM nor improvement in cardiac function in the Phase 2 study. In the immuno-PET study, measurable cardiac uptake of [⁸⁹Zr]Zr-dezamizumab, although seen in both patients, was moderate to low. Uptake was notably lower in the patient with higher LVM. Treatment-associated rash with cutaneous small-vessel vasculitis was observed in both studies. Abdominal large-vessel vasculitis after initial dezamizumab dosing (300 mg) occurred in the first patient with immunoglobulin light chain amyloidosis enrolled in the Phase 2 study. Symptom resolution was nearly complete within 24 h of intravenous methylprednisolone and dezamizumab discontinuation; abdominal computed tomography imaging showed vasculitis resolution by 8 weeks.

Conclusions: Unlike previous observations of visceral amyloid reduction, there was no appreciable evidence of amyloid removal in patients with cardiac amyloidosis in this Phase 2 trial, potentially related to limited cardiac uptake of dezamizumab as demonstrated in the immuno-PET study. The benefit-risk assessment for dezamizumab in cardiac amyloidosis was considered unfavourable after the incidence of large-vessel vasculitis and development for this indication was terminated. Trial registration NCT03044353 (2 February 2017) and NCT03417830 (25 January 2018).

Keywords: Cardiac amyloidosis; Dezamizumab; Immuno-PET; Miridesap; Positron emission tomography; Serum amyloid P component; Systemic amyloidosis.

Objective and design: Perturbations of peripheral T cell homeostasis and dysregulation of the immune response to SARS-CoV-2, especially in severely ill patients, were observed. The aim of this study was to analyze the cytokine producing ability of peripheral blood cells from severely ill COVID-19 patients upon non-specific in vitro stimulation with phytohemagglutinin (PHA). Possible associations of cytokine levels with patients' age and gender, glucocorticosteroid therapy, as well as the trend of the inflammatory process at the time of sampling (increased or decreased) were also analyzed.

Subjects and methods: The study included 23 COVID-19 patients and 17 healthy control subjects. The concentrations of selected Th1/Th2/Th9/Th17/Th22 cytokines were determined using a multi-analyte flow assay kit.

Results: Our results showed that peripheral blood cells from severely ill COVID-19 patients had a much reduced ability to produce cytokines in comparison to healthy controls. When inflammation was raised, blood cells produced more IL-6 and IL-17, which led to increases of some Th17/Th1 and Th17/Th2 ratios, skewing towards the Th17 type of response. The methylprednisolone used in the treatment of patients with COVID-19 influences the production of several cytokines in dose dependent manner.

Conclusion: Our results indicate that the stage of the inflammatory process at the time of sampling and the dose of the applied glucocorticosteroid therapy might influence cytokine producing ability upon non-specific stimulation of T cells in vitro.

Keywords: COVID-19; Cytokine; Glucocorticosteroid; In vitro; Inflammation; Phytohemagglutinin.

Systemic lupus erythematosus (SLE) is an autoimmune disease that may cause vital organ damage. Although not rare for child-onset SLE to have cardiovascular or pulmonary involvement, myocarditis, and pulmonary hypertension are infrequent features and can be life-threatening. In this case report, we describe an 11-year-old girl with SLE who initially presented with fulminant myocarditis pulmonary hypertension, and massive pericardial effusion. Initial immunosuppressive therapy with methylprednisolone pulse therapy, and IVIG were administered, followed by cyclophosphamide, which was ultimately successful, with no residual pulmonary hypertension and no recurrence of myocarditis for over 3 years after the initial episode. Our case highlights the need for clinicians to be aware of systemic lupus erythematosus as a possible diagnostic entity in pediatric patients with severe myocarditis or pulmonary hypertension. Aggressive immunosuppressive therapy should be strongly considered in such cases, as it may lead to good short-term and long-term outcomes.

Keywords: children; myocarditis; pericardial effusion (PE); pulmonary arterial hypertension (PAH); systemic lupus erythematosus (SLE).

Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of immunotherapy. Unlike other immune-related adverse events, CRS triggered by immune checkpoint inhibitors (ICIs) is not well described. The clinical characteristics and course of 25 patients with ICI-induced CRS from 2 tertiary hospitals were abstracted retrospectively from the medical records and analyzed. CRS events were confirmed by 2 independent reviewers and graded using the Lee et al. scale. The median duration of CRS was 15.0 days (Q1; Q3 6.3; 29.8) and 10 (40.0%) had multiple episodes of CRS flares. Comparing the clinical factors and biomarkers in Grades 1-2 and 3-5 CRS, we found that patients with Grades 3-5 CRS had following: (i) had longer time to fever onset [25.0 days (Q1; Q3 13.0; 136.5) vs. 3.0 days (Q1; Q3 0.0; 18.0), p=0.027]; (ii) more cardiovascular (p=0.002), neurologic (p=0.001), pulmonary (p=0.044) and rheumatic (p=0.037) involvement; (iii) lower platelet count (p=0.041) and higher urea (p=0.041) at presentation compared to patients with Grades 1-2 CRS. 7 patients (28.0%) with Grades 1-2 CRS were rechallenged using ICIs without event. 9 patients (36.0%) were treated with pulse methylprednisolone and 6 patients (24.0%) were treated with tocilizumab. Despite this, 3 patients (50%) who received tocilizumab had fatal (Grade 5) outcomes from ICI-induced CRS. Longer time to fever onset, lower platelet count and higher urea at presentation were associated with Grade 3-5 CRS. These parameters may be used to predict which patients are likely to develop severe CRS.

Keywords: cytokine release syndrome; immune checkpoint inhibitors; immune-related adverse events; immunotherapy; tocilizumab.

BACKGROUND Physicians worldwide have been reporting many cases of COVID-19-induced pulmonary fibrosis. We report the case of a 51-year-old Filipino asthmatic woman who developed post-COVID-19 pulmonary fibrosis subsequently treated with Nintedanib. CASE REPORT The patient presented with a 4-day history of flu-like symptoms in September 2020 and was eventually diagnosed with severe COVID-19 pneumonia. Despite receiving Dexamethasone, Tocilizumab, Remdesivir, and multiple antibiotics, there was increasing oxygen requirement, necessitating ICU admission and high-flow nasal cannula (HFNC). An additional course of hydrocortisone was given due to asthma exacerbation, gradually liberating her from the HFNC. A chest CT scan showed extensive parenchymal changes, for which she received methylprednisolone and physical rehabilitation with persistence of respiratory symptoms. After 40 days of hospitalization, she was sent home on oxygen support and Nintedanib. The patient initially had severe dyspnea (Borg Scale 7) with 6-minute walk distance (6MWD) of 295 meters. Pulmonary function showed moderately severe restrictive lung defect at 52% predicted total lung capacity (TLC) and severely reduced DLCO (28% predicted). Chest CT scoring indicated severe lung involvement. One month after Nintedanib treatment, her Borg Scale improved to 4. Her 6MWD, TLC, and DLCO increased to 434 meters, 64% predicted, and 36% predicted, respectively. A chest CT scan showed regressing fibrosis. After 6 months of treatment, her pulmonary function normalized. DLCO remained moderately reduced (59% predicted) but her 6MWD (457 meters) and CT scan results continued to improve. CONCLUSIONS Nintedanib, along with other interventions, may have potentially improved pulmonary function and CT scan findings in a COVID-19 survivor with pulmonary fibrosis 6 months after treatment.

The aim of this study is to assess whether administration of gabapentin and methylprednisolone as "pre-emptive analgesia" in a group of patients above 65 years of age would be effective in complex pain management therapy following total knee arthroplasty (TKA). One hundred seventy patients above 65 years were qualified for the study, with exclusion of 10 patients due to clinical circumstances. One hundred sixty patients were randomly double-blinded into two groups: the study group (80 patients) and the control group (80 patients). The study group received as "pre-emptive" analgesia a single dose of 300 mg oral (PO) gabapentin and 125 mg intravenous (IV) methylprednisolone, while the control received a placebo. All patients received opioid and non-opioid analgesic agents perioperatively calculated for 1 kg of total body weight. We measured (1) pain intensity level at rest (numerical rating scale, NRS), (2) life parameters, (3) levels of inflammatory markers (leukocytosis, C reactive protein CRP), and (4) all complications. Following administration of gabapentin and methylprednisolone as "pre-emptive" analgesia, the NRS score at rest was calculated at 6, 12 (p < 0.000001), 18 (p < 0.00004) and 24 (p = 0.005569) h postoperatively. Methylprednisolone with gabapentin significantly decreased the dose of parenteral opioid preparations (p = 0.000006). The duration time of analgesia was significantly longer in study group (p < 0.000001), with CRP values lower on all postoperative days (1, 2 days-p < 0.00001, 3 days-p = 0.00538), and leukocytosis on day 2 (p < 0.0086) and 3 (p < 0.00042). No infectious complications were observed in the first postoperative days; in the control group, one patient manifested transient ischemic attack (TIA). The use of gabapentin and methylprednisolone as a single dose decreased the level of postoperative pain on the day of surgery, the dose of opioid analgesic preparations, and the level of inflammatory parameters without infectious processes.

Purpose: We report an unusual manifestation of spontaneous globe rupture in a 9 year old male child with dengue hemorrhagic shock syndrome.

Observations: Nine year old male was admitted in the pediatric intensive care unit in a state of altered sensorium secondary to dengue hemorrhagic shock syndrome. Ophthalmic examination revealed proptosis and hemorrhagic chemosis of the right eye. Within two hours of presentation, spontaneous globe rupture with extrusion of intraocular contents occurred in spite of aggressive treatment and intravenous methylprednisolone.

Conclusions and importance: Spontaneous globe rupture in a child with dengue hemorrhagic shock syndrome with such a rapid course is being reported for the first time in literature. Ophthalmologists and pediatricians should be alert regarding vision threatening manifestations related to dengue hemorrhagic shock syndrome.

Keywords: Dengue; Dengue hemorrhagic shock syndrome; Globe rupture; Ophthalmic; Proptosis.

Purpose: To report anterior chamber flare using laser flare photometry and ciliochoroidal detachment using anterior segment optical coherence tomography (AS-OCT) in a new onset acute lupus choroidopathy case.

Observations: A 57-year-old woman with severe nephritis, pleural effusion, and ascites was referred to our ophthalmology clinic for rapid onset of bilateral blurred vision and eyelid swelling. She had a bilateral high-flared, shallow anterior chamber, and bilateral ciliochoroidal detachment, which was revealed using laser flare photometry and AS-OCT. She also had a serous retinal detachment and disc-macular retinoschisis with a thicker choroid and waved Bruch's membrane. Indocyanine green angiography (ICGA) demonstrated partial hypocyanescence in the early phase and multiple hypercyanescent spots at the intermediate to late phase, which are typical of lupus choroidopathy. Systemic lupus erythematosus was diagnosed, and after the administration of pulse methylprednisolone and pulse cyclophosphamide therapies, all eye findings completely resolved in a month, and all other signs and symptoms improved.

Conclusions and importance: Lupus choroidopathy, which is less common than retinopathy, might be under-diagnosed because of its difficult evaluation. Although ICGA is the gold standard for diagnosing lupus choroidopathy, a high flare of the anterior chamber and ciliochoroidal detachment might be different from lupus retinopathy. Laser flare photometry and AS-OCT can be non-invasive, helpful tools for the longitudinal evaluation of the patient's response to therapy.

Keywords: Anterior segment optical coherence tomography; Ciliochoroidal detachment; Flare meter; Laser flare photometry; Lupus choroidopathy; Systemic lupus erythematosus.

Context: The pathological progression in severe Coronavirus Disease 2019 (COVID-19) includes an excessive and unregulated pro-inflammatory cytokine storm. Though the efficacy of corticosteroids like methylprednisolone (MPS) in severe COVID-19 is proven now, its dose and duration are not precise.

Aims: Our study aimed to compare the effect of a standard dose (SD) of MPS (60-120 mg/day) to a high dose (HD) of MPS (>120 mg/day) on the outcome of hospitalized COVID-19 patients.

Settings and design: This study was a cross-sectional study. Patients admitted to AIIMS, Bhopal's intensive care unit (ICU) from July 2020 to March 2021 were enrolled in the study.

Methods and material: The patient's medical records were extracted from the medical record section of the hospital. The primary endpoint was the all-cause mortality during the hospital stay. The secondary endpoints were the need for mechanical ventilation, the use of vasopressors, the occurrence of acute kidney injury (AKI), and secondary infections.

Statistical analysis used: Data were entered in the MS Excel spreadsheet and coded appropriately.

Results: Our data showed that survival, the need for mechanical ventilation, the occurrence of AKI, and secondary bacterial infection are comparable among the two groups with no significant difference. The logistic regression analysis showed that there is a slightly higher risk of death for patients with an acute respiratory distress syndrome (ARDS) receiving HD of corticosteroids compared to SD, though these results were found to be statistically non-significant.

Conclusions: In hospitalized patients suffering from severe COVID-19 pneumonia, an SD of MPS is as effective as an HD of MPS in terms of reduction in mortality and need for mechanical ventilation.

Keywords: COVID-19; Corticosteroid; methylprednisolone; respiratory failure; sepsis.

Purpose: to report a case of Acute Disseminated EncephaloMyelitis (ADEM) occurring after documented SARS-Cov2 infection and flu-like disease.

Observation: A 59-years-old woman presented with progressive visual loss and right leg paresthesia started 6 days earlier when CT scan excluded abnormalities. Visual acuity was OU hand motion with bilateral slow pupillary response and unremarkable ocular extrinsic motility while visual field testing showed diffuse bilateral sensitivity reduction. The patient had also right leg paresthesia and reported a 2-weeks flu-like syndrome 15 days earlier, with nausea, diarrhea, anosmia, ageusia, cough. Brain Magnetic Resonance Imaging revealed bilateral optic nerve enhancement, multiple brain and spine lesions. SARS-CoV-2 PCR tested negative on nasal swab and positive on cerebrospinal fluid. Patient's serum tested positive for anti-SARS-CoV-2 IgG, negative for anti-aquaporin-4 and anti-myelin oligodendrocyte glycoprotein antibodies. A diagnosis of suspect ADEM post SARS-CoV-2 infection was made and treatment with high dose intravenous methylprednisolone (with subsequent prednisone tapering) and immunoglobulins started. Ten days later vision improved to 20/30 RE and 20/25 LE and 3 months later to 20/20.

Conclusion and importance: ADEM may ensue after SARS-CoV-2 virus infection. High suspicious index and prompt aggressive treatment may result in complete vision restauration.

Keywords: Acute disseminated encephalomyelitis; Bilateral optic neuritis; COVID-19.

Kawasaki-like multisystem inflammatory syndrome related to SARS-CoV-2 infection is a well-described condition in children and adolescents (MIS-C) and now also in adults (MIS-A). We report a case of MIS-A in a previously well woman in her mid-30s who presented with vasopressor-dependent shock 2 weeks after initial recovery from suspected SARS-CoV-2 infection, accompanied by fever, vomiting, diarrhoea, weakness, arthralgia, rash, cough and headache. Examination was notable for fever, tachycardia, hypotension, cervical lymphadenopathy, mucocutaneous involvement, neck stiffness, pansystolic murmur and bilateral crepitations. Inflammatory markers were elevated. Echocardiogram showed mitral regurgitation with preserved ejection fraction. She was treated with vasopressors, admitted to the intensive care unit and subsequently required invasive mechanical ventilation. Both PCR and antibodies for SARS-CoV-2 were positive. Treatment with intravenous methylprednisolone and intravenous immunoglobulin was initiated with rapid improvement in clinical condition and inflammatory markers. She has since made a full recovery with normal echocardiogram 8 months later.

Keywords: COVID-19; adult intensive care; cardiovascular medicine; infectious diseases; rheumatology.

Vaccines are one of the most important strategies against pandemics or epidemics involving infectious diseases. With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there have been global efforts for rapid development of coronavirus disease 2019 (COVID-19) vaccine and vaccination is being performed globally on a massive scale. With rapid increase in vaccination, rare adverse events have been reported. Well-known neurological adverse events associated with COVID-19 vaccination include Guillain-Barré syndrome, myelitis, and encephalitis. However, COVID-19 vaccine-related aseptic meningitis has rarely been reported. A 32-year-old healthy man visited our hospital with a complaint of headache for 1 week. He had received the second dose of the BNT162b2 mRNA COVID-19 vaccine 2 weeks before the onset of headache. Since the initial cerebrospinal fluid (CSF) profile suggested viral meningitis, we started treatment with an antiviral agent. However, the symptoms and follow-up CSF profile on day 7 of hospitalization showed no improvement and SARS-CoV-2 IgG antibodies were detected in the CSF. We suspected aseptic meningitis associated with the vaccination and intravenous methylprednisolone (500 mg/day) was administered for 3 days. The symptoms improved and the patient was discharged on day 12 of hospitalization.

Keywords: Adverse reaction; Aseptic meningitis; BNT162b2 mRNA vaccine; COVID-19 vaccine.

Chronic obstructive pulmonary disease (COPD) is a progressive degenerative disease, of which smoking is the main causer. We carried out this study with the aim of exploring the underlying mechanism of methylprednisolone (MP) treating the COPD. To stimulate COPD in vitro, cigarette smoke extract (CSE)was employed to induce human bronchial epithelial cells BEAS-2B. With the help of MTT and Tunel assays, the viability and apoptosis of BEAS-2B cells after indicated treatment were assessed. The levels of inflammatory response and oxidative stress were determined by the changes of markers basing on their commercial kits. Additionally, annexin A1 (ANXA1) expressions at both protein and mRNA levels were assessed with Western blot and Reverse transcription‑quantitative PCR (RT-qPCR). Moreover, the expressions of apoptosis- and formyl peptide receptor 2 (FPR2) receptors and the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) pathway-related proteins were determined with Western blot., related proteins and proteins. As a result, MP up-regulated the ANXA1 expression in CSE-induced BEAS-2B cells. MP enhanced the viability but suppressed the apoptosis, inflammatory response and oxidative stress of CSE-induced BEAS-2B cells via regulating FPR2/AMPK pathway, while ANXA1 knockdown exhibited oppositive effects on them. In conclusion, MP up-regulated ANXA1 to inhibit the inflammation, apoptosis and oxidative stress of BEAS-2B cells induced by CSE, alleviating COPD through suppressing the FPR2/AMPK pathway.

Keywords: ANXA1; FPR2/AMPK pathway; Methylprednisolone; bronchial epithelial cells; chronic obstructive pulmonary disease.

Introduction: Cabozantinib, which was approved by the Food and Drug Administration (FDA) in 2012, is a tyrosine kinase inhibitor widely used in the treatment of metastatic renal cell carcinoma (RCC) and medullary thyroid carcinoma. To date, no ocular adverse events have been reported by the FDA or on the package label. Here, we described a patient with metastatic RCC who developed bilateral optic disc edema after a 4-month course of cabozantinib.

Case description: A 55-year-old ethnic Chinese male with RCC with multiple metastases presented to our department with progressive blurred vision in both eyes for 1 month. He started taking cabozantinib 60 mg once daily 5 months prior to this presentation. Poor visual acuity and bilateral disc edema were then noted. Cabozantinib was discontinued after that, and 3-day pulse steroid therapy with methylprednisolone 1 g/day was given. The optic disc edema subsided gradually with limited improvement in visual acuity.

Conclusion: Bilateral optic edema should be considered as a complication associated with cabozantinib. We propose discontinuation of the treatment in cases such as that, and pulse steroid therapy should be considered if there is no contraindication.

Keywords: cabozantinib; case report; optic disc edema; pulse therapy.

Background: Systemic steroid therapies for Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) have been challenged due to their limited benefits. Whether additional tumor necrosis factor (TNF)-α inhibition provides an optimized approach remains unexplored.

Objective: To investigate the efficacy of TNF-α inhibition combined with a steroid for SJS/TEN and identify potential biomarkers.

Methods: Twenty-five patients with SJS/TEN were recruited and divided into two groups that received either methylprednisolone (N = 10) or etanercept plus methylprednisolone (N = 15). Serum levels of granzyme B, perforin, interferon-γ, interleukin (IL)-6, IL-15, IL-18, macrophage inflammatory protein (MIP)-1α, MIP-1β, and TNF-α were measured by multiplex cytokine analysis kits during acute and resolution phases.

Results: Compared with the steroid monotherapy, the combination therapy significantly shortened the course of initial steroid treatment, acute stage, hospitalization stay, and skin re-epithelialization. Although both therapies significantly reduced IL-15 levels, the combination therapy also resulted in decreased levels of IL-6 and IL-18. While the level of IL-15 was positively correlated with the skin re-epithelialization time in both groups, the level of IL-6 served as an additional marker for disease course in the combination therapy group.

Limitations: The cohort size is relatively small.

Conclusion: Additional TNF-α inhibition to steroid treatment is effective for SJS/TEN.

Keywords: Stevens-Johnson syndrome; TNF-α inhibition; biomarker; cytokine; interleukin-15; interleukin-6; toxic epidermal necrolysis.

Background: In many clinical situations, ordinal scales afford the primary method of semi-quantifying patient outcomes. In the field of multiple sclerosis, the primary ordinal scale is the Expanded Disability Status Scale. Predominant methods of ordinal scale statistical analysis provide a p-value without effect size or rely heavily on the assumption of proportionality of odds, subjecting them to lack of power and error. The Wilcoxon-Manny-Whitney Odds is a statistical method which provides significant information such as p-value, effect size, number needed to treat, confidence intervals, and is largely assumption-free. However, its utility has not been demonstrated in the field of multiple sclerosis.

Methods: Three clinical studies in the field of multiple sclerosis were selected which utilized ordinal scale outcomes at group or individual levels. Data from these studies was extracted using WebPlotDigitizer, and a custom Wilxocon-Mann-Whitney Odds software was applied to each dataset to re-analyze the main outcomes of the studies.

Results: Re-analysis of the manuscript by Muraro et al., 2017 demonstrated that autologous stem cell transplantation for relapsing remitting multiple sclerosis resulted in a 65% chance of improving from any Expanded Disability Status Scale category, although not significant. Re-analysis of the manuscript by Songthammawat et al., 2019 demonstrated chance of improvement with intravenous methylprednisolone and concurrent plasma exchange was 185% versus 32% in intravenous methylprednisolone with add-on plasma exchange, although not significant. Re-analysis of Kister et al., 2012 demonstrated the chances of mobility or cognition scores generally favored decline at every 5-year increment of study, and although statistically significant, these were smaller effect sizes ranging from an 11% chance of improvement to a 66% chance of decline over a 5-year interval.

Discussion: The Wilcoxon-Mann-Whitney Odds simplifies ordinal data analysis with its robust largely assumption-free nature. In the place of numerous statistical tests, this single test provides effect size estimate, number needed to treat, p-values, and confidence intervals. Importantly, the Wilcoxon-Mann-Whitney Odds effect size calculation is intuitively applicable to both individual and population-levels. Further, the Wilcoxon-Mann-Whitney Odds allows intuitive description of the progression of large cohorts over time, and we were able to clearly convey the odds of mobility and cognitive decline over 30 years in a large multiple sclerosis cohort. Overall, the Wilcoxon-Mann-Whitney Odds is a powerful and robust statistical test with significant promise within the field of multiple sclerosis.

Keywords: Multiple sclerosis; Non-parametric; Odds; Statistics; Wilcoxon-Mann-Whitney.

Rationale: Previous treatment for macrophage activation syndrome (MAS) includes high-dose intravenous methylprednisolone along with intravenous immunoglobulin G. If MAS worsened, second-line therapy consisted of anakinra; if the disease remained refractory, third-line therapy with etoposide was considered. In addition, cyclosporine A plays a role in early MAS and in preventing recurrence. Some studies have reported the use of cytokine-targeting agents other than anakinra, such as canakinumab, tocilizumab, abatacept, and tofacitinib.

Patient concerns: The patient with systemic lupus erythematosus (SLE) had an uncommon combination of intermittent fever, hyperferritinemia, hypertriglyceridemia, jaundice, and significantly abnormal liver function test results. The patient reported a history of daily fever of 38 to 39°C, painful oral ulcer, anorexia, abdominal bloating, diarrhea, and malar rash progression for 2 weeks, and jaundice, tea-colored urine, and clay-colored stool for 1 week preceding hospital admission.

Diagnosis: SLE flareups in the patient were initially suspected. However, the final diagnosis was acute respiratory distress syndrome (ARDS) associated with MAS.

Interventions: The treatment included disease-modifying antirheumatic drugs (DMARDs), such as azathioprine, and titrated steroid doses of methylprednisolone (40 mg q8 h) and dexamethasone (15 mg q8 h), after the patient had ARDS and was intubated.Dose-adjusted monotherapy with dexamethasone was found to be effective; this may be attributed to some DMARDs being unsuitable for cytokine storms, that is, some DMARDs may cause complications in cytokine storms.

Outcomes: After dexamethasone 15 mg q8 h treatment, the patient's fever subsided within 2 days, and liver function became normal within 3 weeks. The patient regularly attended scheduled outpatient follow-up visits after discharge. After 2 years, the patient reported no symptoms or signs of SLE with 2 mg/d oral dexamethasone.

Lessons: Early diagnosis of MAS and dexamethasone treatment for MAS with ARDS appear to be crucial for these patients.

Hypophysitis (HP) is a rare disease which develops secondary to chronic or acute inflammation of the pituitary gland and may cause symptoms related to pituitary dysfunction and mass compression. Lymphocytic HP is the most common subtype of primary HP, while xanthomatous HP (XHP) is considered the rarest form, with 35 reported cases, to date. A 35-year-old woman was initially admitted to a Gynecology clinic with a 2-year history of amenorrhea and headache. She was started on cabergoline 0.5 mg twice a week for macroprolactinoma. Due to persistent amenorrhea with low gonadotropins, she was referred to our Endocrinology clinic. Her pituitary function profile revealed panhypopituitarism and a 13×11×12 mm sized sellar mass with diffuse enhancement which sustained toward the infundibulum and dura was observed on the gadolinium-enhanced pituitary MRI. The patient underwent an endoscopic endonasal transsphenoidal approach for tumor resection and thick yellowish fluid draining from the lesion was observed. The histopathological diagnosis was reported as a rupture of an Rathke's cleft cyst and an XHP. The surgery did not improve the symptoms/pituitary functions, however, headache recovered immediately after the first dose of high dose methylprednisolone treatment. The inflammatory process in a xanthomatous lesion may actually be a secondary response to mucous fluid content release from a ruptured cyst, thus recommended to classify XHP as secondary hypophysitis. Since the differentiation of XHP from other pituitary tumors may be challenging preoperatively, surgery is the major diagnostic tool and also, the most recommended therapeutic option.

Keywords: Hypophysitis; Panhypopituitarism; Rathke's cleft cyst; Xanthomatous.

A 68-year-old man was presented with high fever of unknown origin for 3 weeks and non-productive cough for 1 week. A chest computed tomography (CT) scan revealed multiple nodules and ground glass opacities (GGO) in both lungs. The patient was initially diagnosed with hypersensitivity pneumonitis based on the result of bronchoalveolar lavage fluids (BALF). After treatment with methylprednisolone for 2 weeks, the patient's fever recurred, with no resolution of lesions on chest CT. The patient consented to positron emission tomography (PET)/CT. It showed that fluorodeoxyglucose (FDG) metabolism was significantly increased in the spleen, whole skeleton, and both lungs, suggesting a malignant hematological disease. Large B-cell lymphoma was diagnosed by bone marrow puncture and flow cytometry. Transbronchial lung cryobiopsy was performed to evaluate the diffuse lung lesion. Hematoxylin-eosin (HE) staining showed diffuse infiltration of heterotypic cells in the pulmonary interstitial capillaries. Furthermore, immunohistochemical examination results suggested lung infiltration of B lymphohematopoietic system tumors. The patient was finally diagnosed as intravascular large B-cell lymphoma (IVLBCL). IVLBCL with diffuse lung ground glass lesions is very rare and difficult to diagnose. Transbronchial lung cryobiopsy, as an emerging procedure, plays an important role in the diagnosis of interstitial lung disease and has gained popularity for a lower complication rate and acquisition of more tissue samples.

Keywords: Intravascular large B-cell lymphoma (IVLBCL); case report; cryobiopsy; diffuse lung disease.

Alopecia areata (AA) is an autoimmune disease-specific to specific organs mediated by T lymphocytes with hair follicles as targets. Severe AA could be in the form of alopecia universalis (AU). AU therapy is relatively difficult and challenging with varying outcomes. Herein, we reported a case of AU in a 19-year-old man with alopecia in the hairy scalp area, eyebrows, eyelashes, moustache, beard, and axillary hair since 2.5 years ago. The patient's severity of alopecia tool (SALT) score was 100%. The patient was given a combination therapy of 15 mg methotrexate per week and 16 mg methylprednisolone per day orally and topical treatment with minoxidil 5%. Observations after nine months of treatment showed an improvement in the decrease in SALT scores to 41%. However, striae were found after 3rd month of therapy. Systemic combination therapy of methotrexate and low-dose corticosteroids and topical minoxidil 5% in this patient gave responsive results. Performed the hematological examination, liver function levels, blood glucose levels, and cortisol during long-term use of methotrexate and corticosteroids are necessary. The combination of systemic methotrexate and corticosteroids, and topical minoxidil showed promising results in AU. Nevertheless, long-term observation is still needed to monitor the side effects of therapy.

Keywords: alopecia areata; alopecia universalis; corticosteroid; methotrexate; minoxidil.

Toxic epidermal necrolysis (TEN) is a potentially life-threatening dermatologic disorder that erythema and exfoliation of the skin involve more than 30% of the body surface and usually drug related. A 68-year-old male patient who was admitted to the emergency department with the complaint of extensive bullous lesions on his skin was followed up in the intensive care unit (ICU) with the diagnosis of TEN. He had been on multiple anti-inflammatory, antibiotic and analgesic treatment for approximately 20 days due to respiratory tract infection and gout. Methylprednisolone 1 g day 1 was started after the patient's previous treatments were discontinued. The patient was connected to the mechanical ventilator on 11th day due to sepsis and respiratory mucosal involvement. Regression and epithelialisation of skin lesions started after starting cytokine filter treatment on 14th day. The cytokine filter was applied with a renal replacement therapy machine in our patient. Withdrawal of suspected drugs, maintaining an optimal electrolyte balance, sterile care of skin lesions and management in the ICU of specialised centres are essential. Although agents, such as corticosteroids, intravenous immunoglobulins and cyclosporine, are used in the treatment, we think that the use of cytokine filters will contribute to recovery by stopping the cytokine storm in these cases.

Steroid-induced osteonecrosis of the femoral head (SIONFH) is a frequent orthopedic disease caused by long-term or high-dose administration of corticosteroids. Tanshinone I (TsI), a flavonoid compound isolated from Salvia miltiorrhiza Bunge, has been reported to inhibit osteoclastic differentiation in vitro. This study aimed to investigate whether TsI can ameliorate SIONFH. Herein, SIONFH was induced by intraperitoneal injection of 20 μg/kg lipopolysaccharide every 24 h for 2 days, followed by an intramuscular injection of 40 mg/kg methylprednisolone every 24 h for 3 days. Four weeks after the final injection of methylprednisolone, the rats were intraperitoneally administrated with low-dose (5 mg/kg) and high-dose (10 mg/kg) TsI once daily for 4 weeks. Results showed that TsI significantly alleviated osteonecrotic lesions of the femoral heads as determined by micro-CT analysis. Furthermore, TsI increased alkaline phosphatase activity and expressions of osteoblastic markers including osteocalcin, type I collagen, osteopontin, and Runt-related transcription factor 2 and decreased tartrate-resistant acid phosphatase activity and expressions of osteoclastic markers including cathepsin K and acid phosphatase 5. TsI also reduced inflammatory response and oxidative stress and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in the femoral heads. Taken together, our findings show that TsI can relieve SIONFH, indicating that it may be a candidate for preventing SIONFH.