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Background and Aims

The optimal management of ANCA vasculitis patients consists of accurate identification of disease phenotypes, relapses and preventing complications such as infections and cancer. In this study, we pretend to profile the patients with ANCA vasculitis in terms of clinical features with an emphasis on kidney involvement and relapse.

Methods

Patients included in the study will be individuals ≥ 18 years or older, of both sexes, followed in an outpatient internal medicine and nephrology consultation for a period of up to ten years, with an established diagnosis of ANCA associated vasculitis. Statistical analysis was performed using SPSS software.

Results

Fifty-eight patients with ANCA-associated vasculitis were followed, fifty-four with renal involvement. The majority were male (55%), age mean of 61 years. 75.9% MPO positive. 88% had biopsy confirming vasculitis. Renal biopsies were classified into four classes: most patients (50%) had crescentic class, followed by mixed (33%), sclerotic (10.4%) and focal (6.3%). Creatinine at diagnosis was higher for the crescentic and sclerotic types. 17.2% evolved to ESRD and none was submitted to transplant. 20.7% had a relapse, with a mean time between diagnosis and relapse of 4.5 years. Females, GPA and ANCA MPO were the most affected. 5.2% of patients died. 51% of the patients had an infection in the course of the disease, being a major cause of death. 6 patients were diagnosed with cancer, mainly of the skin.

Conclusions

The prognosis of ANCA-associated vasculitis has been transformed in recent years. Once it was a set of acute and fatal conditions, but these disorders are currently considered to be chronic diseases.

Background and Aims

Cryoglobulins are antibodies that precipitate at low temperatures and dissolve after rewarming.

Cryoglobulinemia refers to the presence of circulating cryoglobulins and generally leads to a systemic inflammatory syndrome characterized by fatigue, arthralgia, purpura, ulcers, neuropathy and/or glomerulonephritis.

The disease mainly involves small to medium-sized blood vessels and causes vasculitis due to cryoglobulin-containing immune complexes.

Methods

A review of current literature on the approach to diagnosis, classification and treatment of cryoglobulinemic vasculitis.

Results

Cryoglobulinemia is classified into three types (I, II and III) on the basis of immunoglobulin composition.

Predisposing conditions include lymphoproliferative, autoimmune diseases and hepatitis C virus infection.

The diagnosis of cryoglobulinemic syndrome is predominantly based on the presence of clinical features and laboratorial demonstration of serum cryoglobulins.

The treatment strategy depends on the cause of cryoglobulinemia. For patients with chronic HCV infection, antiviral therapy is indicated. Immunosuppressive or immunomodulatory therapy, including steroids, plasmapheresis and cytotoxic agents, is reserved for organ-threatening manifestations.

Conclusions

In this review, we discuss the main clinical presentations, diagnostic approach and treatment options.

Background and Aims

Recent studies suggest that multiple positivity of antiphospholipid antibodies (aPL) in antiphospholipid syndrome (APS) is more frequently associated with thromboembolic events than a single positive test. EULAR recommendations suggest that aPL profile (high or low risk) is defined by the presence of multiple versus single aPL type, the titre (moderate-high titre vs low) and the persistence of aPL positivity in repeated measurements. aPL might disappear in some patients during follow-up but little is known about thrombotic recurrence risk in those patients in whom anticoagulation withdrawal could be considered.

To identify and include study articles that reported clinical experience of thrombotic APS patients with aPL persistently negative in whom antithrombotic treatment was withdrawn.

Methods

A systematic review was performed and included articles that reported clinical experience of APS patients with aPL persistently negative and that anticoagulation was stopped for that reason

Results

We identified 6 studies. 22 subjects (mean age 35 ± 11 years, 86,3% female) were included into the final analysis. Seventeen patients had thrombosis (1 arterial), 4 were obstetric APS and only patient had both. Regarding aPL profile, fourteen had single positivity, 7 double and one patient was triple positivity. Patients received treatment a median of 72 months (IQR 31-120). After a median of 27,5 months (IQR 13,5-60) of follow-up after anticoagulation withdrawal, no thrombotic events were observed in 95% of patients.

Conclusions

Results seem to suggest that it is possible to discontinue antithrombotic treatment in some patients with low risk aPL profile and primary APS whom aPL became persistently negative overtime.

Background and Aims

Renal involvement in systemic lupus erythematosus (SLE) include several pathological conditions, but mostly, it is associated with immune complex-induced glomerular disease.

Methods

Pauci-immune glomerulonephritis is a rare condition in patients with SLE, so we report two cases.

Results

Case 1: 39 years old female diagnosed previously as having SLE with articular, cutaneous and renal involvement, antinuclear and anti-dsDNA antibodies presense. First renal biopsy disclosed diffuse lupus nephritis (LN) (type IV A/C). It was used to treat with cyclophosphamide and mycophenolate. Due to persistence of a protein/creatinine ratio 400-600 mg/g, normal urinary sediment, high levels of anti-ds DNA antibodies, low levels of C3 and absence of antineutrophil cytoplasmic antibodies (ANCA), another renal biopsy was performed showing class IV-S LN with pauci-immune features by immunofluorescence.

Case 2: 75 years old female diagnosed previously as having SLE with severe thrombocytopenia that required methylprednisolone, immunoglobulins, rituximab, spelenctomy and eltrombopag. Antinuclear, anti-dsDNA and antiphospholipid antibodies presence. First renal biopsy disclosed focal LN (type III A/C), treated with mycophenolate. Due to an increase of the protein/creatinine ratio to 2009 mg/g, normal urinary sediment, high levels of anti-ds DNA antibodies, low levels of C3/C4 and absence of ANCA, another renal biopsy was performed showing class III-S LN with pauci-immune features by immunofluorescence.

Conclusions

Pauci-immune glomerulonephritis have been found to be ANCA positive, but 10–30% of the cases can be ANCA negative. Although LN is widely associated with a full-house pattern in immunofluorescence, it is known that pauci-immune glomerulonephritis is a rare variant of LN, so is important realize renal biopsy.

Background and Aims

Drug-induced myopathy is among the most common causes of muscle disease. An association has recently been described between programmed death-1 (PD-1)/PD-1 ligand (PD-L1) inhibitors and immune-related adverse events (irAE) affecting the muscle. Here, we report the clinical and pathological findings of nineunrelated patients with PD-1 and PD-L1 inhibitors-associated myopathy.

Methods

We retrospectively analyzed 317 muscle biopsies performed for diagnostic purposes from January 2017 to June 2019. Patients were attended in two tertiary centers and muscle biopsies were performed and analyzed by two myologyexperts. Muscle biopsies were frozen in cooled isopenthane, cryostat sectioned and stained. Immunohistochemistry studies were also performed as a routine procedure in our lab.

Results

We identified 9 patients receiving anti-PD-1 or PD-L1 inhibitors consulting for either muscle weakness, asthenia, myasthenic-like syndrome or other muscle related-symptoms, along with biopsy-proven inflammatory myopathy. One had concomitant myocarditis. In most of the cases muscle biopsy showed a marked phenomenon of necrosis, macrophagy and muscle regeneration with perivascular inflammatory infiltrates with a large component of macrophagic cells. A tendency to perifascicular atrophy was also noticed. The expression of MHC class I antigens predominated in the perifascicular zones.Raised muscle enzymes were detected in 7 patients.

Conclusions

A characteristic clinic-pathological pattern, including a myasthenia gravis-like syndrome plus myositis was found in patients receiving PD-1 and PD-1L inhibitors. A large component of macrophages resembling granulomas seems to be the pathological hallmark of the syndrome. Further information is required to understand the wide spectrum of irAE involving the muscle during or after treatment with anti-PD-1 inhibitors, but the pathological picture seems to be characteristic.

Background and Aims

To assess the efficacy of eculizumab in patients with catastrophic antiphospholipid syndrome (CAPS) based on the real-world experience provided by the “CAPS Registry”.

Methods

We analyzed demographic, clinical and immunological data from all the patients included in the “CAPS Registry” treated with eculizumab and additionally we described eculizumab indication, dose, outcome, use of prophylactic vaccines and adverse effects.

Results

The “CAPS Registry” includes 563 patients from whom 21 (3.7%) were treated with eculizumab (mean age 42.1 years (SD=15); 81.0% female; primary APS patients, 71.4%; precipitating factors, 57.1%): Sixteen (76.1%) of them recovered from the episode of CAPS, 4 (19.0%) patients died, and one (4.7%) patient did not show any improvement with eculizumab. There were no recurrences of thrombosis after a median follow up of 10.7 months. Different regimens were used, but the most common was 900mg weekly for four weeks and 1200mg fortnightly. The required duration of treatment remains unclear.

Conclusions

According to the published evidence and our observations, we consider that eculizumab can be used in addition to the standard treatment as an alternative in patients with CAPS.

Background and Aims

Antiphospholipid syndrome (APS) occurs in 1% of cases as catastrophic variant (CAPS), a highly lethal condition characterized by acute onset of multiple thromboses and/or microangiopathy. Aortic involvement is unusual and requires a high suspicion for diagnosis.

Methods

We describe the case of APS who developed acute aorto-iliac occlusion (Leriche syndrome) as CAPS debut. We also performed a review of the literature by Medline and EMBASE databases

Results

A 64-year-old male patient with primary APS history and previous arterial events was on treatment with only clopidogrel. He presented with aortic barrage so he underwent aorto-bifemoral by pass. At day 1 after surgery he developed thrombocytopenia, hemolytic anemia, livedo racemosa, cutaneous necrosis at lower limbs and alveolar hemorrhage. Antiphosholipid antibodies resulted positive at extremely high titer. Blood smear revealed schistocytes>6%. Skin biopsy documented thrombosis of dermal vessels. Treatment with methylprednisolone pulses, anticoagulation and plasma exchanges was started with full recovery.

Eight cases of Leriche syndrome in APS have been described so far: 5 primary forms (PAPS), 1 case associated with relapsing polychondritis. In 2 cases data were missing. In 3 cases aortic barrage represented APS onset manifestation, 4 cases were preceded by arterial thromboses, while none by venous thrombotic events. No proven evolution into CAPS was previously reported.

Conclusions

Aortic occlusion should be suspected in patients with APS and consistent clinical presentation, particularly when other cardiovascular risk factors or history of arterial thrombosis are present. CAPS is a life-threatening complication of surgery in patients with APS and must be systematically excluded in presence of symptoms.

Background and Aims

At onset of SLE some patients present with nonspecific manifestations, therefore they often do not meet the classificatory criteria. Different definition terms (latent lupus, probable lupus, incomplete lupus, potential lupus, among others) have been used to refer to these patients. This study evaluates the applicability of these definition terms in a group of patients with undifferentiated connective tissue disease (UCTD).

Methods

A descriptive and retrospective study was performed. Adult patients diagnosed with UCTD, who did not meet the classification criteria of any defined CTD were included. Terminology was defined according its definition and criteria used for this purpose. Then we applied these terms in every patient. The information was extracted from the medical record, and a database was created to analiyze the results and calculate the proportions.

Results

Fifty-one patients with UCTD were included. All were females, the mean age at onset of the symptoms was 44.8 years and mean follow-up time was 3.8 years. After comparing classification criteria and definitions, all the patients meet the definition of "latent lupus", while only 92,08% meet the definition of "probable lupus", "incomplete lupus" and "potential lupus". No other relevant differences were found.

Conclusions

The difference between the patients who met the definition of "latent lupus" compared to other definitions is due to the inclusion of variables such as Raynaud's phenomenon and alopecia included only in this term. Finally, the term UCTD seems to be the most appropriate to define patients who have manifestations suggestive of SLE but do not meet classification criteria.

Background and Aims

Few published studies have investigated the correlations between systemic sclerosis (SSc) and the metabolic syndrome (MetS), but one Mexican study has reported that the prevalence of MetS in SSc patients is 36.4%. The aim of this cross-sectional observational study was to evaluate the prevalence of MetS in patients with SSc, and investigate the correlations between the MetS and the clinical and laboratory variables of SSc.

Methods

MetS was diagnosed on the basis of the 2005 criteria of the National Cholesterol Education Program and the International Diabetes Federation, and SSc on the basis of the 2013 ACR/EULAR classification criteria.

Results

We enrolled 57 patients with SSc (54 women, 94.7%, mean age + SD 62.43 ± 14.60 years and a mean disease duration of 16.47 ± 10.22 years: 32 patients (56.1%) had diffuse SSc. Fifty-four patients (94.7%) were positive for ANA, 17 (29.9%) for anti-centromere antibodies, and 27 (47.4%) for anti-SCL70 antibodies. Eleven patients (19.3%) were affected by SMet. Six patients (10.5%) were affected by type 2 diabetes mellitus, 29 (50.8%) by arterial hypertension, 21 (36.8%) by dyslipidemia, and eight (14%) by hyperuricemia. Two patients (3.5%) were obese, and 28 (49.1%) overweight. There was no statistically significant association between MetS and the demographic, clinical or laboratory variables of SSc, but there was a statistically significant association with cardiac arrhythmia (p=0.037).

Conclusions

Our findings show that 19.3% of the SSc patients were affected by MetS in the absence of any statistically significant association with the clinical or laboratory characteristics of the disease other than cardiac arrhythmia.