Survival and outcomes of tocilizumab use in severe and critically ill Covid-19 patients not responding to steroids

BackgroundMortality and morbidity are highest in severe and critically ill patients with COVID -19 pneumonia. Recently corticosteroids have shown a definite mortality benefit in these patients. In this study we used interleukin -6 inhibitor, tocilizumab in patients who failed to show any clinical improvement after initial treatment with steroids.Patients and methodsThis is a retrospective observational study conducted at a tertiary care referral hospital in India. Severe and critical COVID 19 patients, who got admitted to intensive care unit and subsequently received tocilizumab were included. Patients who worsened clinically or had no change in oxygen requirement even after 24hrs of receiving Intravenous methylprednisolone at a dose of 1-2mg/kg/day received a maximum total dose of 800mg of intravenous tocilizumab. The day 28 all cause mortality and progression to mechanical ventilation were the primary outcome measures. Clinical improvement and oxygen requirements after tocilizumab administration along with trends in inflammatory markers were secondary outcome. Secondary infections rates and other drug related side effects were also noted.ResultsA total of 51 patients who did not show clinical improvement even after 24 hours of intravenous steroids and received tocilizumab were included. In these patients, there was a significant decrease in oxygen requirement by day 3 and clinical improvement by day 7 of tocilizumab administration. Among the inflammatory markers, we observed elevated median baseline values of CRP (114.2 mg/L), IL-6 (55.4 pg/ml) and Neutrophil to Lymphocyte Ratio (12.4). Out of these only CRP showed a significant decrease after the drug administration. 13 (26.5%) of the 49 patients who were on non-invasive or conventional oxygen support progressed to mechanical ventilation. The day 28 all-cause mortality rate was 10/51(19.6%). 10(19.6%) of the 51 patients had life threatening infections, 5/51 had thrombocytopenia, 3/51 had pneumo-mediastenum/pneumothorax, 1 patient had colonic perforation and 1 patient had transaminitis following tocilizumab administration.ConclusionEarly and timely administration of tocilizumab only in selected severe and critical covid patients not responding to initial steroids appears to increase the survival. Further randomized controlled trials are required to confirm this finding.

Monitoring of Patients with Autoimmune Cytopenias during Sars-Cov-2 Vaccination Campaign: The Experience of a Reference Center

SARS-CoV-2 infection and vaccination have raised concern in immune mediated diseases, including autoimmune cytopenias (AIC, i.e. autoimmune hemolytic anemia, AIHA; autoimmune thrombocytopenia, ITP; autoimmune neutropenia, AIN; aplastic anemia, AA; and their combination, termed Evans syndrome, ES). The latter are highly heterogeneous conditions with variable severity and a clinical course marked by several relapses often triggered by immune-activating events (infections, traumas, surgery, etc.) including vaccines. Some reports of ITP and AIHA post-SARS-CoV-2 vaccines have been described but no population studies have been conducted in AIC patients. Here we systematically studied a large series of 100 patients with AIC (44 AIHA, 38 ITP, 7 AIN, 6 ES, and 5 AA) prospectively followed at a reference center in Milan, Italy, who underwent SARS-CoV-2 vaccination from 24 th of March until the end of June 2021. Patients (median age 62 years, range 25-89, female/male ratio 1.7) were monitored with whole blood counts and LDH testing the week before and the week after each vaccination dose. Importantly, ongoing AIC therapy (38% of cases, including steroids, cyclosporine, eltrombopag, and complement inhibitor sutimlimab) were kept stable within the 2 weeks before vaccination. Patients mainly received Pfizer-BioNtech vaccine (N=88), followed by Moderna (N=10), and Astra-Zeneca (N=2). Table 1 summarizes hematologic trends and side effects observed after each dose in patients with ITP and AIHA. Regarding the former, a delta percentage reduction of 10% or higher was observed in up to 13% of cases after the first and the second dose, requiring therapy adjustment in 2 patients. They were two elderly male subjects on low dose eltrombopag treatment and experienced a severe/moderate relapse (platelets 28 and 21x10^9/L) with mucosal bleeding, after the 2 nd dose of Pfizer vaccine. Both had a concomitant trigger (1 hip fracture and 1 bronchitis reactivation) and were rescued by increasing eltrombopag dose and with the addition of prednisone 1 mg/Kg day. Regarding AIHA, 3 elderly patients experienced a clinically significant relapse (>10% Hb decrease): 1 female patient experienced an Hb reduction from 10.4 to 9.1 g/dL after the first dose of Pfizer vaccine, that required a slight increase of steroid dose (to 5 mg day prednisone) and remained stable after the second dose; 1 male subject had an Hb reduction from 13.9 to 9.1 g/d>L after the first dose of Moderna vaccine, requiring prednisone 0.5 mg/kg day; the third male patient experienced a severe relapse (Hb reduction by 47%, from 14 to 7.4 g/dL) with LDH increase to 2.3 x ULN after the second dose of Pfizer vaccine. The patient required high dose intravenous steroids and hemolysis improved in about 1 week. All patients had warm type AIHA and had complained no other triggers or non-hematologic adverse events. Patients with AIN, AA and ES had no significant changes in their hematologic values (1 AIN had a neutrophil decrease by 30% but was consistent with previous oscillations; 2 ES had a platelet or neutrophil decrease within the normal range) and required no treatment changes. Finally, the following non-hematologic adverse events were observed: fever (7%), pain at the injection site (15%) and arthralgia (<5%), without significant differences between the first and the second dose. These data show that SARS-CoV-2 vaccination may be associated with a mild decrease of hematologic values in about 10% of AIC cases. However, true ITP and AIHA relapses occurred in 5% of cases only, sometimes in the presence of a concomitant trigger, and were rapidly rescued with treatment adaptation. Overall, the hematologic monitoring of SARS-CoV-2 vaccine adopted in our survey appears appropriate to early detect and manage AIC reactivation, ensuring a safe vaccination campaign in this patient population. Figure 1 Figure 1. Disclosures Fattizzo: Annexon: Consultancy; Alexion: Speakers Bureau; Kira: Speakers Bureau; Momenta: Honoraria, Speakers Bureau; Novartis: Speakers Bureau; Apellis: Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Bianchi: Agios pharmaceutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Barcellini: Novartis: Honoraria; Bioverativ: Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals: Honoraria; Agios: Honoraria, Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees.

Severe ataxia uncovered Hodgkin’s lymphoma: do not forget CT neck when looking for covert malignancy

A 53-year-old woman without medical problems presented with 5-month history of dizziness, difficulty speaking, severe ataxia, which worsened a day before admission to inability to stand unsupported. An extensive workup was initiated to find the cause of ataxia. The laboratory investigations and imaging of the brain and whole spine revealed no lesions. She was found to have autoimmune thyroiditis, positive coeliac disease antibodies without clinical features and vitamin D deficiency. No intravenous steroids or immunosuppressive therapy was given. Cerebrospinal fluid showed lymphocytic pleocytosis. The workup for the cause of severe ataxia revealed an oropharyngeal lesion with cervical lymph nodes, and the biopsy showed classical Hodgkin’s lymphoma of mixed cellularity. She was treated with chemotherapy followed by radiation therapy and made a remarkable recovery, and currently, she is in remission without distant metastases, 5 years after the initial diagnosis. Her neurological status improved, and she remained with mild ataxia.

Refractory Bell’s palsy responding to late treatment with high-dose intravenous steroids

Bell’s palsy is an acute peripheral facial paralysis with no detectable cause. Although the prognosis of Bell’s palsy is generally good, some patients experience poor recoveries and there is no established treatment for those that do not recover even after receiving the conventional treatment. Here we present two cases of refractory Bell’s palsy with facial nerve enhancement in magnetic resonance imaging who showed symptomatic improvement after the late administration of high-dose intravenous methylprednisolone.

Therapeutic Effect of Superficial Cryotherapy versus Intralesional Corticosteroids injection in Alopecia Areata

Alopecia areata, one or more round bald patches appear suddenly, most often on the scalp. It can affect males and females at any age. It starts in childhood in about 50%, and before the age of 40 years in 80%. The exact mechanism is not yet understood. There is not yet any reliable cure for alopecia areata. Several topical treatments used for alopecia areata are reported to result in temporary improvement in some people. Their role and efficacy are unknown. Injections of triamcinolone acetonide 2.5–10 mg/ml into patchy scalp, its efficacy is temporary. Oral and pulse intravenous steroids in high dose can lead to temporary regrowth of hair. The sensitisers diphenylcyclopropenone provoke hair growth in treated areas Now, superficial cryotheray is introduced as a possible treatment for Alopecia Areata. With minimial side effects and being less painful. So, this study clarifies the therapeutic efficacy and safety of superficial cryotherapy for treatment of patchy Alopecia areata. Aim of the study The aim of the study is to evaluate and compare the efficacy and safety of Superficial Cryotherapy and Intralesional corticosteroids in the treatment of patchy Alopecia Areata. Patients and methods study included 20 patients complaining of Alopecia Areata. 3 patches of scalp alopecia areata will be randomly subjected to either superficial cryotherapy twice monthly for 3 months (3 cycles, 2-3 seconds) or intralesional steroid injections once monthly for 3 months (triaminoclone acetonide 1:7, 1ml) or intralesional saline (1 ml). Assessment for the response to treatment will be done at one month and three month following treatment by digital photography and by phototrichogram by comparing number of Terminal, and vellus and hair thickness, Also assessment for side effects of therapy will be done. Results Patients treated with TCA showed statistically significant high response compared to patients treated with cryotherapy. Also, side effects assessment showed minimal side effects with treatment with TCA compared to cryotherapy. Conclusion TCA treatment of alopecia areata is much tolerable than treatment with cryotherapy with also better response rates.

Sjögren-related cardiomyopathy presenting with cardiogenic shock

Previous reports have described non-ischaemic cardiomyopathy related to a variety of autoimmune diseases. However, very few case reports describe Sjögren disease as a contributing factor to cardiomyopathy. We report the case of a 69-year-old woman with a history of Sjögren disease who presented with cardiogenic shock. Laboratory testing and cardiac MRI revealing apical septal late gadolinium enhancement were consistent with an autoimmune aetiology. After ruling out ischaemic, infectious and other possible causes, the patient’s clinical presentation was thought to be related to underlying Sjögren disease. She was treated with intravenous steroids and evidence-based heart failure therapy, but she eventually died after having declined heart transplantation. Given the rarity of Sjögren disease, no diagnostic criteria or standard treatment has been established for cardiomyopathy related to this disease. Diagnosis should be considered in patients who show evidence of autoimmune processes after other possible causes are ruled out.

Immunoglobulin G4-related Ophthalmic Disease with Peripheral Eosinophilia and Elevated Immunoglobulin E Levels

Purpose: To report a case with peripheral eosinophilia and elevated immunoglobulin (Ig) E levels, subsequently diagnosed as IgG4-related ophthalmic disease involving the extraocular muscles.Case summary: A 56-year-old male visited the allergy department presenting with systemic urticaria and bilateral eyelid swelling that began 5 months prior. Laboratory examinations showed elevated levels of serum eosinophil and IgE, 1,309 IU/uL and 1,793 IU/mL, respectively. Orbital computed tomography revealed that all extraocular muscles and the bilateral exophthalmos were enlarged, and the patient was referred to the ophthalmology department. Eye alignment was orthophoric for all gaze directions, and limited abduction (-1) was noted in both eyes. An incisional biopsy of the extraocular muscles was conducted. Histopathological findings showed lymphoid aggregates, diffuse fibrosis, and an increased IgG4+/IgG+ plasma cell ratio of 40%, which led to the diagnosis of IgG4-related ophthalmic disease. An elevated IgG4 serum level (1,710 mg/dL) was also noted. The patient received high-dose intravenous steroids and eyelid swelling improved after two months. Levels of serum eosinophil, IgE, and IgG4 all decreased after three months.Conclusions: IgG4-related ophthalmic disease may be accompanied by eosinophilia and elevated IgE. These findings may facilitate future diagnoses of this disease.

A Case of Chronic Relapsing Inflammatory Optic Neuropathy

Chronic relapsing inflammatory optic neuropathy (CRION) is a recently described form of recurrent isolated subacute optic neuropathy, with accumulating evidence that it is a nosological distinct entity. The condition is highly responsive to systemic steroid treatment and prone to relapse on steroid withdrawal. Diagnosis and management of this condition is often challenging. This 33-year-old lady with family history of multiple sclerosis (MS), with uniocular visual loss of her right eye since 2 years old without apparent cause, presented with reduction of vision and loss of colour vision in the left eye, associated with painful eye movement. There was internuclear ophthalmoplegia but slit lamp examination were unremarkable. She had no other related sensory or motor symptoms. Magnetic resonance imaging (MRI) did not reveal any features of MS. Aquaporin-4 antibody, anti-MOG and gene testing for Leber’s hereditary optic neuropathy were all negative. Metabolic, infective, and other autoimmune causes were also excluded. Visual evoked potential studies of left eye showed a mild reduction in amplitude with no prolongation of latency. Her multiple optic neuritis recurrences were treated with intravenous steroids followed by tapering regime of oral prednisolone with good effect. Knowledge of this rare condition as part of the differential diagnoses of possible aetiologies of optic neuropathy is important among Ophthalmologists, as prompt diagnosis and steroid treatment helped reduce the associated risk of blindness. Multiple relapses after initial successful treatment of inflammatory optic neuropathy should raise the suspicion of CRION.International Journal of Human and Health Sciences Supplementary Issue-2: 2021 Page: S19

Retrobulbar neuritis associated with empty sella syndrome: A diagnostic challenge

A 35-year-old female presented with sudden diminution of vision to finger counting at half meters in right eye (RE) since 15 days. RE showed grade III RAPD. Rest of the ocular examination was normal. She had no significant past medical history. Neuroimaging showed empty sella. We suspected retrobulbar neuritis (RBN) as a cause of loss of vision since there was no evidence of acute change in morphology of sella turcica like hemorrhage, trauma or ischemia, furthermore there were no pathological findings in RE and visual cortex to explain acute visual loss. Therefore, we prescribed intravenous steroids followed by oral steroids. Vision in RE improved to 6/12 after 15 days. We found that RBN can be a cause of sudden vision loss in cases with empty sella syndrome (ESS) and can pose diagnostic challenge that whether the vision loss is due to ESS or RBN. RBN can be a cause of acute vision loss in patients with ESS and can create diagnostic confusion.

Confabulation, amnesia and motor memory loss as a presentation of apparent ITPR1 antibody autoimmune encephalitis

A 59-year-old woman presented to the hospital with acute, hypoactive altered mental status. Her symptoms had begun 3 days prior when she developed hallucinations, urinary and faecal incontinence, and somnolence. She also exhibited confabulations, amnesia, motor memory loss and a wide-based gait. Medical, psychiatric and neurological evaluations including imaging and laboratory workup were unrevealing. Treatment for possible Wernicke encephalopathy and psychosis with high-dose intravenous thiamine and antipsychotic medications did not lead to improvement. After discharge, a send-out cerebrospinal fluid autoimmune encephalitis panel resulted positive for the newly identified neuronal inositol triphosphate receptor one (ITPR1) antibody. This prompted readmission for intravenous steroids, plasmapheresis and intravenous immunoglobulin, which yielded mild clinical improvement. Here, we describe confabulations and psychiatric symptoms as novel manifestations of the primary presentation of anti-ITPR1 encephalitis in an effort to promote faster recognition of this disease and early initiation of treatment in suspected cases.