Tom 58 (2020): Zeszyt 1 (March 2020)

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. Diabetic neuropathy (DN) is one of the most devastating complications of diabetes mellitus; however, in contrast to other countries, there are no scientific studies in Portugal evaluating the impact of demographic and clinical characteristics of this pathological entity. The aim of this study was to evaluate the impact of gender, metabolic control, age of diabetic patients, as well as time of disease progression, the appearance of complaints related to neuropathic pain.

Material and methods. A multicentre study with a non-probabilistic, convenience sample of 359 patients was performed employing the quantitative method, using the Statistical Package for Social Science 24 software. The p-value of p < 0.05 was defined to consider a result statistically significant. The Spearman correlation coefficient (r) was determined to determine the relationship between categorical variables.

Results. There was no statistically significant difference in the prevalence of DN between genders (p = 0.633 and r = 0.025). There was a statistically significant relationship between the value of HbA1c and DN, with p = 0.010 and r = 0.136. There is a relationship between age and complaints of neuropathic pain, with p = 0.034 and r = 0.112. The variable, time of disease progression, is also correlated with the appearance of complaints of neuropathic pain with p = 0.020 and r = 0.112.

Conclusion. The prevalence of neuropathic pain in subjects with diabetes is not negligible and is associated with modifiable risk factors that can be identified, possibly modified and prevented. The correct approach for these patients, which involves screening and early treatment, is decisive improving functionality and quality of life.

Introduction. The purpose of this study was to compare the role of the thrombophilic variants among two groups of high risk patients with vascular disorders and recurrent pregnancy loss.

Methods. 200 patients, including 76 with thrombotic accidents and 124 with two or more idiopathic recurrent miscarriage during the first trimester, were tested for the presence of Factor V (F V) Leiden G1691A, Factor II (F II) G20210A, plasminogen activator inhibitor (PAI) 4G/5G, and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms using Real time polymerase chain reaction (RT – PCR) in the Laboratory of Medical Genetics, Varna, Bulgaria between June 2016 and May 2019. Frequencies of thrombophilic gene polymorphisms were compared among the two populations and to the expected genotype frequencies.

Results. Individuals with a history of vascular disorders had a significantly higher frequency of F V Leiden variant compared to women with recurrent miscariage. There was no statistical difference between the analyzed patients for the other three thrombophilic polymorphisms. The allelic frequencies and the expected genotype frequencies of the F V, F II and MTHFR polymorphisms were calculated according to Hardy-Weinberg equilibrium. The percentages of the homozygotes for F V and F II were higher than expected in the two groups of patients. For the MTHFR there was no difference.

Conclusion. F V Leiden remains the strongest risk factor for vascular disorders and recurrent pregnancy loss. Screening for this variant should be recommended to patients with thrombotic accidents and women with repeated miscarriage. The role of F II, PAI and MTHFR remains controversial.

Introduction. Familial Mediterranean Fever (FMF) is an autoinflammatory disease. Prolidase is a specific imidodipeptidase that plays a role in collagen degradation, and an important role in inflammation and wound healing. Hypoxia-inducible factor-1α (HIF-1) is an important protein in the regulation of immunological response, hemostasis, vascularization. The aim of the study was to compare serum prolidase and HIF-1α levels in patients with FMF in attack-free period and healthy control group.

Methods. Between August 2017 and December 2017, sixty patients diagnosed with FMF according to the criteria of the Tel-hashomer and admitted to Sivas Cumhuriyet University Medical Faculty, Internal Medicine Rheumatology Department and sixty healthy volunteers were enrolled in the study.

Results. Median serum prolidase levels were 72.1 (25.1–114.9) ng/ml in FMF group and 30.7 (21.3–86.2) ng/mL in healthy control (HC) group (p = 0.018). ROC analysis showed that the sensitivity was 65% and the specificity was 68.3% at serum prolidase levels 54.03 ng/mL (p < 0.05). The median serum levels of HIF-1α in the FMF group was 482.0 (292.0–3967.0) pg/mL and 632.0 (362.0–927.0) pg/mL in the HC group (p > 0.05). There was no significant correlation between laboratory findings, sex, age, and prolidase (p > 0.05).

Conclusion. Serum prolidase enzyme levels in FMF patients with attack-free period were significantly higher than in the HC group. However, the role of prolidase and HIF1-α in the FMF disease needs to be clarified with more extensive and comprehensive studies.

Introduction. Warfarin is one of the most frequently used anticoagulant agents in the clinic. The most important adverse effect of warfarin is hemorrhage of vital organs, such as lung and brain. Diffuse Alveolar Hemorrhage (DAH) is a rare clinical condition which occurs due to variety of medical disorders. Although it’s rarely reported, DAH can be a result of coagulopathy prompted by warfarin therapy. In this study we present a case of DAH, caused by warfarin toxicity which referred to the hospital with non-specific respiratory symptoms.

Case presentation. A 41-year-old female patient referred to the hospital complaining of shortness of breath, cough and dizziness. She had been taking warfarin due to mitral valve replacement for the past 10 years. Her recent symptoms began shortly after taking amoxicillin, a few days before admission. Early clinical examination and paraclinical studies reveal DAH as the cause of respiratory symptoms. The patient was then intubated and received fresh frozen plasma, packed cells and oral vitamin K. Laboratory findings apart from increased INR, PT, ESR and CRP were all within normal range. After the initiation of treatment patient’s INR decreased and her clinical condition improved. Follow-up CT-Scan and bronchoscopy also confirmed resolving DAH.

Conclusions. The usage of warfarin in anticoagulation should be closely monitored due to its narrow therapeutic window and other factors, including its interaction with other medications such as antibiotics. Warfarin toxicity can lead to DAH, a life-threatening condition which can be presented with non-specific symptoms and deteriorate patient’s clinical condition in a short time. Therefore, it is of utmost importance to watch closely for primary symptoms of such rare incident in patients under warfarin therapy and initiate treatment as soon as possible, to prevent mortality.

Introduction. Although type 1 diabetes mellitus is largely associated with autoimmune thyroid disease and this entity has been recently referred to as autoimmune polyglandular syndrome type 3 variant, the autoimmune polyglandular syndrome type 3 variant in patients with rheumatoid arthritis has not been reported so far. We herein describe the first case of rheumatoid arthritis that was associated with autoimmune polyglandular syndrome type 3 variant.

Case report. A 77-year-old woman with a 15-year history of rheumatoid arthritis (RA) and a 10-year history of type 2 diabetes mellitus (T2D) presented with polyarthralgia and hyperglycaemia. Methotrexate 16 mg/week had been started from the onset and was continued, and adalimumab 40 mg/day was started for RA. Insulin treatment was also started for the diabetes. Laboratory examinations revealed high levels of C-reactive protein (CRP), rheumatoid factor, anti-cyclic citrullinated peptide antibody, and matrix metalloprotease 3. She was admitted multiple times as the symptoms recurred after treatment. Subsequently, based on the clinical course and investigations, she was diagnosed with type 1 diabetes mellitus and Graves’ disease occurring during the course of RA and T2D. Her clinical course improved after reinforcement of insulin therapy and the addition of thiamazole therapy.

Conclusion. In patients with rheumatoid arthritis, the autoimmune polyglandular syndrome type 3 variant should be considered as the cause of the deterioration.