High dose subcutaneous Anakinra to treat acute respiratory distress syndrome secondary to cytokine storm syndrome among severely ill COVID-19 patients.

OBJECTIVE: Severely ill COVID-19 patients may end in acute respiratory distress syndrome (ARDS) and multi-organ failure. Some of them develop a systemic hyperinflammatory state produced by the massive release of inflammatory agents, known as cytokine storm syndrome (CSS). Inhibition of IL-1 by Anakinra (ANK) is a potential life-saving therapy for severe CSS cases. We propose a rationale for the use of subcutaneous ANK and review our initial experience in a small cohort of severe COVID-19 CSS patients. METHODS: Retrospective cohort study of COVID-19 patients developing ARDS (PaO2/FiO2 <300) and exhibiting signs of hyperinflammation (ferritin >1000 ng/mL and/or d-dimers > 1.5 µg/mL, plus IL-6 < 40 mg/mL) that received ANK. For comparison, a propensity score matched historical cohort of patients treated with IL-6 inhibitor Tocilizumab (TCZ) was used. Patients had previously received combinations of azithromycin, hydroxy-chloroquine, and methyl-prednisolone. Laboratory findings, respiratory function and adverse effects were monitored. Resolution of ARDS within the first 7 days of treatment was considered a favorable outcome. RESULTS: Subcutaneous ANK (100 mg every 6 h) was given to 9 COVID-19 ARDS CSS patients (77.8% males). Median age was 62 years (range, 42 to 87). A TCZ cohort of 18 patients was selected by propensity score matching and treated with intravenous single dose of 600 mg for patients weighing >75 Kg, or 400 mg if < 75 Kg. Prior to treatment, median PaO2/FiO2 ratio of the ANK and TCZ cohorts were 193 and 249, respectively (p = 0.131). After 7 days of treatment, PaO2/FiO2 ratio improved in both groups to 279 (104-335) and 331 (140-476, p = 0.099) respectively. On day 7, there was significant reduction of ferritin (p = 0.046), CRP (p = 0.043), and IL-6 (p = 0.043) levels in the ANK cohort but only of CRP (p = 0.001) in the TCZ group. Favorable outcome was achieved in 55.6% and 88.9% of the ANK and TCZ cohorts, respectively (p = 0.281). Two patients that failed to respond to TCZ improved after ANK treatment. Aminotransferase levels significantly increased between day 1 and day 7 (p = 0.004) in the TCZ group. Mortality was the same in both groups (11%). There were not any opportunistic infection in the groups nor other adverse effects attributable to treatment. CONCLUSION: Overall, 55.6% of COVID-19 ARDS CSS patients treated with ANK exhibited favorable outcome, not inferior to a TCZ treated matched cohort. ANK may be a potential alternative to TCZ for patients with elevated aminotransferases, and may be useful in non-responders to TCZ.

Giant cell arteritis with spontaneous remission.

The case of a 75-year-old woman diagnosed with polymyalgia rheumatica (PMR), treated with low doses of prednisone, and with clinical and analytical remission is reported. Two years later, she presented with a clinical picture of giant cell arteritis (GCA), including headache, diplopia, jaw pain, feeling of swelling in both temples, and elevation of acute phase reactants. Symptoms spontaneously subsided 2 weeks later, while analytical parameters improved without any treatment. A high-resolution colour Doppler ultrasound showed thickening of the intima-media complex with 'halo' sign in the right temporal artery. A biopsy of the right temporal artery was performed, although it was not successful, as no artery could be found, and the procedure became more complicated with an eyebrow ptosis due to a lesion in the frontal branch of the facial nerve. GCA diagnosis was based on the clinical, laboratory, and ultrasound findings. The patient was treated with prednisone and methotrexate, without clinical or analytical relapse. Comments are presented on the described cases of GCA with spontaneous remission, and the most appropriate treatments in these cases are discussed. Other peculiarities of the case, such as the progression to GCA more than 2 years after the onset of PMR, and the complications from the temporal artery biopsy are also mentioned.

Psoriatic arthritis: interaction between cardiometabolic diseases and inflammatory burden of the disease.

BACKGROUND AND OBJETIVES: Psoriatic arthritis is accompained by several cardiometabolic comorbidities. Obesity causes a low-grade systemic inflammation and is a negative predictor of treatment response. We wanted to evaluate if there are interactions between metabolic status, inflammatory parameters and disease activity; and whether metabolic or cardiovascular diseases have any association with the reduction of the inflammatory burden by treating the psoriatic arthritis. MATERIAL AND METHODS: We have carried out a cross-sectional descriptive study of 160 patients with psoriatic arthritis. Sociodemographic, clinical and analytical variables were collected, as well as the presence of dactylitis and enthesitis; and HAQ, DAPSA and Minimal Disease Activity criteria. Chi-square test and the H of Kruskall Wallis were used to carry out comparisons, considering P < .05 as statistically significant. To establish correlations, Pearson correlation coefficient was used. RESULTS: BMI and waist circumference correlate with CRP and ESR (significance: < .05) although the correlation strenght is low (Pearson <.4), but there is no such relationship with DAPSA or meeting MDA criteria. Using biologic therapies is associated with a lower prevalence of cardiovascular events (P = 0.047; OR: 0.12, 95% CI: 0.01-0.9) and enthesitis (P = .008; OR: 0.3, CI 95%: 0.16-0.56); and normal levels of CRP (P = .029; OR: 0.25, 95% CI: 0.07-0.87) and ESR (P = 0.024; OR: 0.36, 95% CI: 0.16-0.82) when comparing to conventional therapies. DISCUSSION AND CONCLUSIONS: Anti-TNFα treatment could reduce cardiovascular risk in patients with psoriatic arthritis. There may be higher levels of CRP and ESR in obese individuals without this necessarily implying higher disease activity.

Psoriatic arthritis: interaction between cardiometabolic diseases and inflammatory burden of the disease. / Artritis psoriásica: interacción entre enfermedades cardiometabólicas y la actividad inflamatoria de la enfermedad.

BACKGROUND AND OBJETIVES: Psoriatic arthritis is accompained by several cardiometabolic comorbidities. Obesity causes a low-grade systemic inflammation and is a negative predictor of treatment response. We wanted to evaluate if there are interactions between metabolic status, inflammatory parameters and disease activity; and whether metabolic or cardiovascular diseases have any association with the reduction of the inflammatory burden by treating the psoriatic arthritis. MATERIAL AND METHODS: We have carried out a cross-sectional descriptive study of 160 patients with psoriatic arthritis. Sociodemographic, clinical and analytical variables were collected, as well as the presence of dactylitis and enthesitis; and HAQ, DAPSA and Minimal Disease Activity criteria. Chi-square test and the H of Kruskall Wallis were used to carry out comparisons, considering P<.05 as statistically significant. To establish correlations, Pearson correlation coefficient was used. RESULTS: BMI and waist circumference correlate with CRP and ESR (significance: <.05) although the correlation strenght is low (Pearson<.4), but there is no such relationship with DAPSA or meeting MDA criteria. Using biologic therapies is associated with a lower prevalence of cardiovascular events (P=0.047; OR: 0.12, 95% CI: 0.01-0.9) and enthesitis (P=.008; OR: 0.3, CI 95%: 0.16-0.56); and normal levels of CRP (P=.029; OR: 0.25, 95% CI: 0.07-0.87) and ESR (P=0.024; OR: 0.36, 95% CI: 0.16-0.82) when comparing to conventional therapies. DISCUSSION AND CONCLUSIONS: Anti-TNFα treatment could reduce cardiovascular risk in patients with psoriatic arthritis. There may be higher levels of CRP and ESR in obese individuals without this necessarily implying higher disease activity.

Carbamazepine-induced systemic lupus erythematosus: A case-based review.

A case of carbamazepine-induced systemic lupus erythematosus (CBZ-DILE) is presented, along with a literature review, with the aim to define the clinical and serological characteristics of this group, and compare them with systemic lupus erythematosus (SLE) triggered by other drugs (DILE). A 31-year-old woman presented with a 6-month history of hand arthritis and nasal ulcers. She had been diagnosed with epilepsy at 12 years of age and had continued treatment with carbamazepine (CBZ) for the past 18 years with excellent clinical control. Laboratory data revealed antinuclear antibodies (ANA) positive to a titer of 1/1280, and positive anti-nucleosome antibodies. The patients' clinical symptoms disappeared after the CBZ discontinuation and did not reappear during the 1-year follow-up period. A search was made in the PubMed/Medline database of the (CBZ-DILE) published cases. A total of 26 cases of CBZ-DILE were found in the search. CBZ-DILE cases are characterized by variable latency periods that often last for years and are not related to the dose of CBZ. Most frequent clinical findings of CBZ-DILE in patients are arthralgia/arthritis, mucocutaneous manifestations, constitutional symptoms, and pleuritis or pericarditis. The renal involvement has not been reported in CBZ-DILE. Antihistone antibodies were observed less frequently, and anti-dsDNA antibodies were observed more frequently than in the "classic" DILE. The ANA remained positive in over 60% of cases during the follow-up after withdrawal. The CBZ-DILE has significant clinical and laboratory manifestations that distinguish it from classic DILE or idiopathic SLE.

Severe Guillain-Barré syndrome in a patient receiving anti-TNF therapy. Consequence or coincidence. A case-based review.

The adverse effects of anti-tumour necrosis factor alpha (TNFα) drugs include an increase in the risk of infections, congestive heart failure, lupus-like syndrome, and the onset or worsening of various demyelinating diseases such as, multiple sclerosis, optic neuritis, and Guillain-Barrè syndrome (GBS), among others. We describe the case of a patient who developed GBS while she was on treatment with adalimumab. A 50-year-old woman with rheumatoid arthritis (RA) was admitted to the hospital due to progressive severe bilateral symmetric weakness of the legs, which quickly extended to the upper limbs and to the respiratory muscles. Adalimumab was started 13 months before. GBS was diagnosed and the anti-TNFα therapy discontinued. The serological test for Campylobacter jejuni was positive. She required invasive mechanical ventilatory support for 9 months. Twelve months later, the patient was using a wheelchair following a rehabilitation programme, and at 24 months she was walking a few steps with assistive devices. The relevant literature on the relationship between GBS and anti-TNFα is reviewed. Twenty three cases of GBS occurring during anti-TNFα therapy have been reported so far in the literature. In several cases, there was no clear temporal association, more than half had a possible previous infection, and in two cases the drug was reintroduced without recurrence of GBS. Our case, which is best explained by C. jejuni infection, as well as some of the cases described are probably not a direct result of anti-TNFα treatment, but an accidental coincidence. We also discuss the potential therapeutic options after anti-TNFα discontinuation.