Backgroud. Which factors determine venous thrombotic events in some antiphospholipid syndrome (APS) patients and arterial thrombosis or conditions related to pregnancy in others has not been established yet. Purpose. The aim of this study was to search the antiphospholipid antibodies (APLAs) correlates in regard to deep vein thrombosis (DVT) in patients with systemic lupus erythematosus (SLE) and APS. Methods. Twenty-nine patients fulfilling the criteria of both SLE and APS were included. Complete anamnesis and clinical examination was performed on inclusion. Also, for all patients, disease activity was assessed by the SLEDAI score. An extended APLAs profile, ten Abs, was searched. Results. The titers of IgG anticardiolipin (aCL), IgG anti-β2 glycoprotein I (aβ2GPI), IgG antiphosphatidylethanolamine (aPE), and also of IgG antiprothrombin (aPT) were significant higher in patients with DVT history. After analysis by ROC curve and univariate logistic regression, the strongest association was found for IgG aPE. Also, in multivariate analysis, SLEDAI score correlated with the DVT antecedents. Conclusions. IgG aPE might be involved in DVT pathogenic pathways in patients with SLE and APS as their titers remain significantly higher in patients with previous DVT. Lupus patients with DVT events represent a subgroup of patients with more severe underlying pathology.
Background. Over the past years, eosinophil infiltration involving the gastrointestinal tract and pancreas leading to eosinophilic pancreatitis, eosinophilic gastroenteritis and hypereosinophilic syndrome has been reported in the literature.
We aimed to analyze and compare the features involving patients with eosinophilic pancreatitis and pancreatitis associated with eosinophilic gastroenteritis and to determine if there is a connection between the two disorders or if they in fact meet the diagnostic criteria for hypereosinophilic syndrome.
Material and methods. The following search was performed in March 2019 on PubMed (MEDLINE) database using the medical terms “pancreatitis”, “eosinophilic pancreatitis”, “eosinophilic gastroenteritis” and “hypereosinophilic syndrome”.
Results. The search revealed 119 publications from 1970 onwards. A total of 83 papers were excluded, and the remaining 36 publications, consisting in case reports and case series, were analyzed. From 45 patients, 20 subjects with eosinophilic gastroenteritis developed pancreatitis, 20/45 had eosinophilic pancreatitis, and 5/45 hypereosinophilic syndrome involving the pancreas. There was no significant difference regarding clinical, laboratory and imaging features between the three groups, despite the multiple theories that explain the association of pancreatic and gastrointestinal eosinophilic infiltration. Although there was a strong resemblance between the three groups, histological evidence of eosinophilic gastrointestinal infiltration guided the treatment towards a less invasive way, while subjects with eosinophilic pancreatitis underwent pancreatic surgery to exclude potentially malignant lesions.
Conclusion. Although there are various theories that explain pancreatitis development in patients with eosinophilic gastroenteritis, hypereosinophilia diagnostic work-up should be taken into account in all patients with high number of blood eosinophils, even in those with eosinophilic pancreatitis in order to establish the diagnosis using a minimally invasive approach and to apply an adequate treatment.
Giant cell arteritis is a common systemic vasculitis affecting the elderly, with maximum prevalence in the 7th decade of age, targeting aortic derived medium and large vessels of the neck and head. Diagnosis is established on a biopsy specimen of the temporal artery wall, through pathological confirmation of panarteritis, typically characterized by mononuclear cell infiltrate, with the 1990 ACR criteria often used in clinical practice.
We present the case of a patient with a new onset headache and systemic inflammation, who did not fulfil the classical diagnostic criteria, nor did the temporal artery biopsy (TAB) provide a positive result. However, the ultrasonographical features, clinical evolution and response to corticosteroid therapy confirmed the diagnosis. This patient had bilateral presence of the halo sign on color duplex ultrasonography (CDUS), cited as a highly specific feature, when compared to the ACR criteria as a standard reference. We employed its positive likelihood-ratio (LR+) of 43 as previously estimated, while considering a low pre-test probability for a positive diagnosis (15%), to calculate a post-test probability of 88%, leading to our decision to treat him as having giant cell arteritis. Remission of the headache and rebound phenomena when tapered off steroid therapy substantially contributed to the positive diagnosis, underlining the importance of future studies needing to use clinical evolution as a reference standard.
Introduction. Macrophage activation syndrome (MAS) is a life-threatening hyperinflammatory state mediated by uncontrolled cytokine storm and haemophagocytosis. Although rarely reported, MAS might occur in systemic lupus erythematosus (SLE), notably as an inaugural manifestation. Glucocorticoids (GCs) are the cornerstone of SLE therapy. However, in some cases high doses of GCs are required to achieve remission (i.e. glucocorticoid-resistance), leading to significant side effects.
Case report. A 28-year-old Romani male was admitted to our hospital for polyarthralgia, polyserositis and fatigability. The patient had high-grade fever, jaundice and generalized lymphadenopathy. Laboratory tests revealed severe mixed hemolytic autoimmune anemia, leukopenia, hepatocytolysis, coagulation abnormalities, hypertriglyceridemia, biological inflammatory syndrome, hyperferritinemia and persistent proteinuria of nephritic pattern. Imaging studies showed pleuropericardial effusion, hepatosplenomegaly and polysynovitis. Additional blood tests revealed hypocomplementemia and positive ANA, anti-dsDNA and anti-Sm antibodies. Haemophagocytosis was not identified either on bone marrow or axillary lymph node biopsy specimens. However, SLE-associated MAS seemed to fit this set-up. High-dose corticotherapy (6.5 g methylprednisolone followed by prednisone, 1.5 mg/kg/day after discharge) and intravenous cyclophosphamide were necessary to induce and sustain remission.
Conclusion. MAS is a potentially severe manifestation that should be considered at SLE onset whenever high fever and elevated serum levels of aspartate aminotransferase, lactate dehydrogenase, C-reactive protein, ferritin and procalcitonin are noted. Early diagnosis and prompt treatment lead to remission in two thirds of cases.
Glucocorticoid-resistance leads to the use of high-dose corticotherapy or immunosuppressive agents that could elicit serious side effects. New insights into the molecular mechanisms of glucocorticoid-resistance are needed in order to conceive more adequate GC-therapies.
Background. In the last years an uprising interest for a relatively unknown entity, eosinophilic ascites (EA), has been recorded.
Our aim is to investigate the potential causes of EA development, as well as clinical, laboratory, endoscopic and radiologic features, management and outcome in these patients.
Methods. The following research was performed on PubMed (MEDLINE) database using the medical subject headings [Mesh] terms “Ascites” AND “Eosinophils”.
Results. A total of 284 results, dating from 1962 onwards, were found and abstracts were examined. 131 papers were excluded and the remaining 153 publications, consisting in case reports and series of cases, were analyzed.
From 171 patients with EA, 127 subjects (74%) had EGE, 17 (10%) parasitic and fungal infections, 11(7%) Hypereosinophilic syndrome and 16 patients (9%) less common diseases (eosinophilic pancreatitis, chronic eosinophilic leukemia, myelofibrosis, T-cell lymphoma, Churg Strauss Syndrome, Systemic lupus erythematosus, Familial paroxysmal polyserositis and Ménétrier’s disease). High eosinophil blood count and IgE levels as well as gastrointestinal symptoms are frequent. The diagnosis is based on ascitic fluid analysis, imaging and endoscopic biopsies. Therapy with corticosteroids results in resolution of eosinophilic ascites in almost all patients.
Conclusion. In most cases, in the absence of allergy, parasitic infections, malignancy, hematological disorders, peritoneal tuberculosis, inflammatory bowel disease or autoimmune disease, EA develops as a manifestation of eosinophilic gastroenteritis.
Obesity is a growing health burden worldwide, increasing the risk for several diseases featuring the metabolic syndrome – type 2 diabetes mellitus, dyslipidemia, non-alcoholic fatty liver disease and cardiovascular diseases. With the increasing epidemic of obesity, a new pathologic condition has emerged as a component of the metabolic syndrome – that of non-alcoholic fatty pancreas disease (NAFPD). Similar to non-alcoholic fatty liver disease (NAFLD), NAFPD comprises a wide spectrum of disease – from deposition of fat in the pancreas – fatty pancreas, to pancreatic inflammation and possibly pancreatic fibrosis. In contrast with NAFLD, diagnostic evaluation of NAFPD is less standardized, consisting mostly in imaging methods. Also the natural evolution of NAFPD and its association with pancreatic cancer is much less studied. Not least, the clinical consequences of NAFPD remain largely presumptions and knowledge about its metabolic impact is limited. This review will cover epidemiology, pathogenesis, diagnostic evaluation tools and treatment options for NAFPD, with focus on practices for clinicians.
The purpose of this paper is to present a case of congenital pseudohypoparathyroidism, late diagnosed in a 22-year-old patient.
The patient’s history revealed hypocalcaemia, diagnosed at birth and persistent despite the treatment with calcium. At 8 years old, the patient is diagnosed with epilepsy and receives treatment with Levetiracetam and Oxcarbazepine; at 12 years old she is diagnosed with dilatative cardiomyopathy and receives treatment with Spironolactone and Glycosides. At 22 years old, she visits our Internal Medicine Department with the suspicion of polymyositis and psoriasis. Clinical examination shows armonic short stature, fourth finger hypoplasia, laboratory findings show severe hypocalcaemia, the hand X-ray - third and fourth metacarpal hypoplasia, immunological tests were negative. All data leads to the diagnosis of congenital disease, and given the history of the patient and the evolution of the clinical manifestations we presume hypoparathyroidism or pseudohypoparathyroidism, therefore PTH is dosed – with normal values, and the diagnosis of congenital pseudohypoparathyroidism is established. The patient was referred to endocrinology, where genetic tests were performed to confirm the diagnosis.
In conclusion, in the absence of multiple pathology integration into a single disease, the diagnosis of the genetic disease is delayed. Therefore, it is important to have a comprehensive approach and collaboration between different specialties to establish the correct diagnosis.
Background: Systemic sclerosis (Ssc) is an autoimmune disease characterized by graduate cutaneous and tissue fibrosis development and irreversible fibroproliferative vascular changes. The aim of the current systematic review was to update the list of proteomic candidate biomarkers identified from Ssc samples with mass spectrometry techniques.
Methods: Medline and Scopus databases were searched on 1st September 2020. Relevant articles were searched from March 2014 until September 2020. Two independent reviewers evaluated the retrieved articles.
Results: From a total of 97 articles, 9 articles were included in the final analysis summarizing 539 candidate proteomic biomarkers from various samples from Ssc patients (a larger number compared to the previous systematic review). Most biomarkers were identified from cutaneous biopsies. Only 5 articles included a validation step of the findings with only 13 biomarkers being validated.
Conclusions: Although many candidate biomarkers were additionally identified, independent validation studies are needed in order to evaluate the importance of these biomarkers for Ssc patients.
Background. Sjogren’s syndrome (SS) is among the most frequent autoimmune diseases and one of its most severe extraglandular manifestations is peripheral neuropathy. There is no consensus about peripheral neuropathy treatment in SS. Our aim is to identify studies proving the efficiency of immunosuppressive treatment on peripheral neuropathies in SS.
Methods. The search was conducted on the PubMed (MEDLINE) database. Studies with patients diagnosed with SS and peripheral neuropathy were included. Treatment with one of the following was among inclusion criteria: glucocorticoids (GC), rituximab (RTX), azathioprine (AZA), mycophenolic acid (MMF), cyclophosphamide (CP), methotrexate (MTX), plasmapheresis or iv immunoglobulins (IV IG).
Results. A total of 116 results were found and abstracts were examined. 103 papers were excluded, and the remaining 13 papers were analyzed. They were 3 case series and 10 case reports, retrospective, totalizing 62 patients of which 22 (35.5%) received IV IG, 8 (13%) received RTX, 7 (11%) CP, and 5 (8%) received only GC. Drug associations containing corticosteroids were frequent. Of those 22 treated with IV IG, 18 patients improved (82%), and 4 stabilized (18%).
IV IG was useful in sensory, motor and sensorimotor neuropathies. CP had good results in mononeuritis multiplex, while autonomic neuropathies responded well to GC or RTX. AZA, RTX, MTX, MMF or plasmapheresis were not used alone. Follow-up periods were heterogenous and the evaluation of the neuropathy was not systematic.
Conclusion. There is only low level evidence (retrospective case reports and case series). In most cases, IV IG treatment in patients with peripheral neuropathies and SS resulted in clinical improvement, while other therapies, such as RTX, corticosteroids and CP proved to be useful in a handful of cases.
Introduction. COVID-19 disease was associated with both thrombo-embolic events and in-situ thrombi formation in small vessels. Antiphospholipidic antibodies were found in some studies.
Aim. Assessment of protein S activity in patients with COVID-19 as a cause of this prothrombotic state, and of the association of protein S activity with worse outcome.
Methods. All patients admitted for COVID-19 disease in a university hospital between 15th of May and 15th of July 2020 were prospectively enrolled into this cohort study. Patients treated with antivitamin K anticoagulants and with liver disease were excluded. All patients had protein S activity determined at admission. The main outcome was survival, while secondary outcomes were clinical severity and lung damage.
Results. 91 patients were included, of which 21 (23.3%) died. Protein S activity was decreased in 65% of the patients. Death was associated with lower activity of protein S (median 42% vs. 58%, p < 0.001), and the association remained after adjustment for age, inflammation markers and ALAT. There was a dose-response relationship between protein S activity and clinical severity (Kendall_tau coefficient = –0.320, p < 0.001; Jonckheere-Terpstra for trend: p < 0.001) or pulmonary damage on CT scan (Kendall_tau coefficient = –0.290, p < 0.001; Jonckheere-Terpstra for trend: p < 0.001). High neutrophil count was also independently associated with death (p = 0.002).
Conclusion. Protein S activity was lower in COVID-19 patients, and its level was associated with survival and disease severity, suggesting that it may have a role in the thrombotic manifestations of the disease.