A 76-year-old man with bronchial asthma was admitted for respiratory failure and bloody sputum. A significant drop in haemoglobin and multiple consolidations supported clinical diagnosis of diffuse alveolar haemorrhage (AH). Myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) was positive and urinalysis suggested glomerulonephritis. Based on eosinophilia, sinusitis, peripheral nerve involvement, and leukocytoclastic vasculitis, he was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) associated with AH. Our case-based review suggested that male predominance (65%), high positivity for ANCA (88%), and a high frequency of renal involvement (45%) may be characteristic of AH in EGPA. Although AH is rare in EGPA, we should be aware of this life-threatening complication.

We here report the first case of anti-proteinase 3-positive anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis following the severe acute respiratory syndrome coronavirus 2 Pfizer-BioNTech vaccine presenting with prominent liver involvement and alveolar haemorrhage. Two weeks after vaccination, a 49-year-old man developed inflammatory arthralgias and hypertransaminasaemia. Two months later, fever and haemoptysis appeared; the patient tested positive for anti-proteinase 3 autoantibodies. High-dose steroids and rituximab were started, and complete remission was achieved. Systemic autoimmune diseases, including ANCA-associated vasculitis, should always be considered in the differential diagnosis of hypertransaminasaemia, especially when the clinical context is suspicious.

Progress in the study of Covid-19 disease in rodents has been hampered by the lack of angiotensin-converting enzyme 2 (ACE2; virus entry route to the target cell) affinities for the virus spike proteins across species. Therefore, we sought to determine whether a modified protocol of lipopolysaccharide (LPS)-induced acute respiratory distress syndrome in rats can mimic both cell signalling pathways as well as severe disease phenotypes of Covid-19 disease. Rats were injected via intratracheal (IT) instillation with either 15 mg/kg of LPS (model group) or saline (control group) before being killed after 3 days. A severe acute respiratory syndrome (SARS)-like effect was observed in the model group as demonstrated by the development of a \"cytokine storm\" (>2.7 fold increase in blood levels of IL-6, IL-17A, GM-CSF, and TNF-α), high blood ferritin, demonstrable coagulopathy, including elevated D-dimer (approximately 10-fold increase), PAI-1, PT, and APTT (p < 0.0001). In addition, LPS increased the expression of lung angiotensin II type I receptor (AT1R)-JAK-STAT axis (>4 fold increase). Chest imaging revealed bilateral small patchy opacities of the lungs. Severe lung injury was noted by the presence of both, alveolar collapse and haemorrhage, desquamation of epithelial cells in the airway lumen, infiltration of inflammatory cells (CD45+ leukocytes), widespread thickening of the interalveolar septa, and ultrastructural alterations similar to Covid-19. Thus, these findings demonstrate that IT injection of 15 mg/kg LPS into rats, induced an AT1R/JAK/STAT-mediated cytokine storm with resultant pneumonia and coagulopathy that was commensurate with moderate and severe Covid-19 disease noted in humans.

Background: Despite many studies on COVID-19, our knowledge of it remains incomplete. In some cases, treating SARS-CoV-2 infection concomitant with other diseases can be particularly challenging, as finding an appropriate treatment may involve some risks. Case presentation: A 34-year-old SARS-CoV-2 positive patient admitted due to fever, dyspnoea, haemoptysis and pneumonia, developed alveolar haemorrhage and acute kidney injury. Due to his severe state, abnormalities in laboratory tests and rapidly progressing loss of kidney function, kidney biopsy, as well as antibody panel were carried out, in which perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) were found with a high titer (>200; N: <1:20). The results of kidney biopsy, combined with clinical manifestation and laboratory findings prompted the diagnosis of rapidly progressing glomerulonephritis (RPGN) in the course of p-ANCA vasculitis. Initial treatment consisted of heamodialyses, remdesivir, plasmaphereses, intravenous immunoglobulins, antibiotics, corticosteroids and fraxiparine. Once the haemorrhage had subsided, kidney function had been partially retrieved and heamodialyses had no longer been necessary, cyclophosphamide treatment was initiated, despite being contraindicated in COVID-19 according to its summary of product characteristics. Immunotherapy is still continued. The patient has already received a total of 2.4g of cyclophosphamide (4 cycles of 600mg each every three weeks). Pulmonary and radiological regression, as well as improvement of renal parameters have been achieved.        Conclusions: We suspect that cyclophosphamide, the drug of choice in p-ANCA vasculitis, could be a potential factor providing regression of the radiological changes in the lungs and it could have prevented the patient from developing acute respiratory distress syndrome. COVID-19 diagnosis should not exclude searching for other diseases which can have a similar course. When treating a patient in a life-threatening condition, a departure from trying to find the perfect timing of cyclophosphamide delivery should be considered, as delaying it could cause potentially greater harm.

Tobacco has long been known to be one of the greatest causes of morbidity and mortality in the adults, but the effects on the foetus and young children, which are lifelong, have been less well appreciated. Developing from this are electronic nicotine delivery systems or vapes, promulgated as being less harmful than tobacco. Nicotine itself is toxic to the foetus, with permanent effects on lung structure and function. Most vapes contain nicotine, but they also contain many other compounds which are inhaled and for which there are no toxicity studies. They also contain known toxic substances, whose use is banned by European Union legislation. Accelerating numbers of young people are vaping, and this does not reflect an exchange of vapes for cigarettes. The acute toxicity of e-cigarettes is greater than that of tobacco, and includes acute lung injury, pulmonary haemorrhage and eosinophilic and lipoid pneumonia. Given the worse acute toxicity, it should be impossible to be complacent about medium and long term effects of vaping. Laboratory studies have demonstrated changes in lung proteomics and the innate immune system with vaping, some but not all of which overlap with tobacco. It would be wrong to consider vapes as a weaker form of tobacco, they have their own toxicity. Children and young people are being targeted by the vaping industry (which is largely the same as the tobacco industry), including on-line, and unless an efficient legislative program is put in place, a whole new generation of nicotine addicts will result.
UNASSIGNED: Santrauka. Seniai žinoma, kad tabakas yra viena iš dažniausių suaugusiųjų sergamumo ir mirštamumo priežasčių, tačiau visam gyvenimui pėdsakus paliekantis tabako poveikis vaisiui, kūdikiui ir vaikui išnagrinėtas mažiau. Dar mažiau žinoma apie santykinai neseniai atsiradusias elektronines nikotino tiekimo sistemas – elektronines cigaretes, kurios tariamai yra mažiau kenksmingos nei „tradicinis“ tabako rūkymas. Nikotinas yra toksiškas žmogaus vaisiui – jis turi ilgalaikį poveikį plaučių augimui, struktūrinei ir funkcinei brandai. Daugumos elektroninių cigarečių sudėtyje randama nikotino, tačiau jose taip pat yra kitų įkvepiamųjų junginių, kurių naudojimas ribojamas Europos Sąjungoje, taip pat junginių, kurių toksiškumo tyrimai dar nėra iki galo atlikti. Kai kurie pokyčiai, tačiau ne visi, sutampa su „tradicinio“ tabako rūkymo sukeliamais pokyčiais. Elektroninių cigarečių ūminis toksiškumas yra didesnis nei įprastų cigarečių – tai atspindi dokumentuoti ūminio plaučių pažeidimo, kraujavimo į alveoles, taip pat eozinofilinės bei lipoidinės pneumonijos atvejai. Atsižvelgiant į didesnį ūminį toksiškumą, vidutinio ir ilgalaikio elektroninių cigarečių rūkymo poveikis kelia nerimą. Laboratoriniai tyrimai atskleidė su elektroninių cigarečių rūkymu susijusius grėsmingus plaučių proteomikos ir įgimtos imuninės sistemos pokyčius. Būtų neteisinga laikyti elektronines cigaretes lengvesne įprastų cigarečių rūšimi, nes elektroninės cigaretės pasižymi tik joms būdingu toksiškumu. Elektroninių cigarečių pramonė nusitaikė į internetu pasiekiamus vaikus ir jaunimą, rūkančių jaunų žmonių skaičius didėja sparčiausiai. Jeigu bus delsiama sukurti veiksmingą teisinio užkardymo sistemą, išaugs nauja priklausomybės nuo nikotino karta. Raktiniai žodžiai: ūminis plaučių pažeidimas, kraujavimas į alveoles, eozinofilinė pneumonija, lipoidinė pneumonija, įgimta imuninė sistema, nikotinas, elektroninės cigaretės, rūkymas, EVALI, vaikai.

Clinicians should be aware that interstitial shadows with extreme hypertension should be considered as indicators for diffuse alveolar haemorrhage due to pheochromocytoma crisis.

UNASSIGNED: Early diagnosis of diffuse alveolar haemorrhage (DAH) can be extremely difficult, as the common clinical picture is often attributed to more common clinical conditions. High degree of suspicion is key to diagnosis which can be much more difficult during the coronavirus disease 2019 (COVID-19) pandemic.
UNASSIGNED: A 61-year-old man with inferolateral ST-segment elevation myocardial infarction treated by a stent to the left circumflex artery and intravenous abciximab treatment was started for the high thrombus burden. Two hours later, the patient developed dyspnoea and hypoxaemia. Chest examination revealed diffuse rales over both lung fields. Chest X-ray revealed bilateral diffuse alveolar infiltrates, while the echocardiography was normal. Chest computed tomography (CT) was performed and the \'crazy paving appearance\', which is the typical radiological finding of COVID-19, was reported. The patient was considered to be suspected of COVID-19 and was transferred to a quarantine unit. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test was obtained and azithromycin and hydroxychloroquine were initiated. 48 h later, 2.6 mmol/L reduction was observed in haemoglobin levels and haemoptysis was developed. After the second negative RT-PCR with an interval of 24 h, CT was repeated and the patient was diagnosed to have abciximab-induced DAH. The patient was later followed up conventionally and discharged after two weeks without additional complications.
UNASSIGNED: DAH and COVID-19 might share common clinical and radiological findings during examination. The physicians must be aware of the high motivation of the COVID-19 pandemic which can lead to misdiagnosis by overlooking other important clinical conditions.

Plasma exchange (PLEX) is capable of removing significant amounts of circulating antibodies. In anti-neutrophil cytoplasmic antibody-associated vasculitis, PLEX was reserved for patients with severe presentation forms such as rapidly progressive glomerulonephritis and pulmonary haemorrhage. The Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis (PEXIVAS) trial included all comers with a glomerular filtration rate <50 mL/min/1.73 m2 and thus aimed to answer the question of whether PLEX is an option for patients with no relevant kidney function impairment or not. PEXIVAS revealed that after a follow-up of almost 3 years, routine administration of PLEX does not provide an additional benefit to reduce the rate of a composite comprising end-stage kidney disease or death. In the absence of histological parameters, it is tempting to speculate whether PLEX is effective or not in those with a potential for renal recovery. A subset of patients presented with alveolar haemorrhage, and there was a trend towards a better outcome of such cases receiving PLEX. This would be in line with observational studies reporting a recovery of alveolar haemorrhage following extracorporeal treatment. In this PRO part of the debate, we highlight the shortcomings of the PEXIVAS trial and stimulate further research paths, which in our eyes are necessary before abandoning PLEX from the therapeutic armamentarium.

An 81-year-old man complaining of exertional dyspnoea underwent coronary angiography using an iodinated contrast medium. After angiography, the patient required systemic corticosteroid therapy because of respiratory failure due to alveolar haemorrhage. Percutaneous coronary intervention was performed 29 days after angiography using the same contrast medium. After the intervention, the patient required intubated mechanical ventilation and renal replacement therapy. Bronchoalveolar lavage was bloody with many haemosiderin-filled macrophages. Systemic corticosteroid therapy again improved his clinical condition. Iodinated contrast media may cause alveolar haemorrhage and re-exposure to contrast media may induce a more severe adverse reaction.
UNASSIGNED: Iodinated contrast media may cause alveolar haemorrhage.Re-exposure to iodinated contrast media may induce a more severe adverse reaction.

BACKGROUND: Alemtuzumab is a humanized anti-CD 52 monoclonal antibody approved as a disease-modifying therapy for active relapsing-remitting Multiple Sclerosis (MS). Alemtuzumab has been associated with several adverse effects, including infusion-associated reactions, infections, acquired autoimmune diseases, and malignancies.
METHODS: We report a case of Alemtuzumab-induced simultaneous onset of autoimmune haemolytic anaemia, alveolar haemorrhage, nephropathy and stroke in a 52-year-old man that occurred 8 months after initiation of alemtuzumab. The laboratory testing was consistent with autoimmune haemolytic anaemia. Computed tomography of the chest and bronchoscopy revealed an alveolar haemorrhage. Stroke workup revealed acute infarcts in bilateral occipital territories.
CONCLUSIONS: This is the first case report of a simultaneous onset of autoimmune haemolytic anaemia, alveolar haemorrhage, nephropathy, and ischaemic stroke after the first alemtuzumab course in relapsing-remitting MS patient. This case highlights the potential for the co-occurrence of unexpected and potentially life-threatening complications of alemtuzumab therapy necessitating rigorous monitoring once prescribed.