Successful Desensitization to Sorafenib and Imatinib-A Report of Two Cases and a Literature Review.

BACKGROUND: Drug desensitization allows for safe administration of a drug to a patient with a previous hypersensitivity reaction. Successful desensitization protocols have been described for different medications, including protocols for oncology patients. Few cases of desensitization to sorafenib and imatinib have been described in the literature so far. OBJECTIVE: The objective of this paper is to describe the process of the sorafenib and imatinib drug hypersensitivity diagnosis and desensitization process in two patients. METHODS: Two oncology patients who experienced non-immediate hypersensitivity reactions to sorafenib and imatinib underwent desensitization to these drugs. We designed a protocol for the first patient and used a modified protocol from the literature for the second patient. RESULTS: By using a slow desensitization technique and gradual tapering of corticosteroids and antihistamines, both patients reached the target dose of the incriminated drug. CONCLUSIONS: Desensitization to sorafenib and imatinib can be an effective therapeutic option in patients with hypersensitivity to those medications, without alternative treatment options.

Case report: Rapidly progressive neurocognitive disorder with a fatal outcome in a patient with PU.1 mutated agammaglobulinemia.

Introduction: PU.1-mutated agammaglobulinemia (PU.MA) represents a recently described autosomal-dominant form of agammaglobulinemia caused by mutation of the SPI1 gene. This gene codes for PU.1 pioneer transcription factor important for the maturation of monocytes, B lymphocytes, and conventional dendritic cells. Only six cases with PU.MA, presenting with chronic sinopulmonary and systemic enteroviral infections, have been previously described. Accumulating literature evidence suggests a possible relationship between SPI1 mutation, microglial phagocytic dysfunction, and the development of Alzheimer's disease (AD). Case description: We present a Caucasian female patient born from a non-consanguineous marriage, who was diagnosed with agammaglobulinemia at the age of 15 years when the immunoglobulin replacement therapy was started. During the following seventeen years, she was treated for recurrent respiratory and intestinal infections. At the age of 33 years, the diagnosis of celiac-like disease was established. Five years later progressive cognitive deterioration, unstable gait, speech disturbances, and behavioral changes developed. Comprehensive microbiological investigations were negative, excluding possible infective etiology. Brain MRI, 18FDG-PET-CT, and neuropsychological testing were suggestive for a diagnosis of a frontal variant of AD. Clinical exome sequencing revealed the presence of a novel frameshift heterozygous variant c.441dup in exon 4 of the SPI1 gene. Despite intensive therapy, the patient passed away a few months after the onset of the first neurological symptoms. Conclusion: We describe the first case of PU.MA patient presenting with a rapidly progressive neurocognitive deterioration. The possible role of microglial dysfunction in patients with SPI1 mutation could explain their susceptibility to neurodegenerative diseases thus highlighting the importance of genetic testing in patients with inborn errors of immunity. Since PU.MA represents a newly described form of agammaglobulinemia, our case expands the spectrum of manifestations associated with SPI1 mutation.

Asthma Inflammatory Phenotypes: How Can We Distinguish Them?

BACKGROUND AND OBJECTIVES: induced sputum is used to assess different inflammatory phenotypes in asthma, but is not used routinely. We aimed to determine the proportion of inflammatory asthma phenotypes based on induced sputum, to find biomarkers that can discriminate between phenotypes, and to evaluate biomarkers in patients with and without biological therapy in different inflammatory asthma phenotypes. MATERIALS AND METHODS: this cross-sectional study investigated clinical characteristics, asthma control tests, skin prick test, impulse oscillometry (IOS), spirometry, induced sputum, biomarkers (IgE, eosinophils, fractional exhaled nitric oxide (FeNO), serum periostin, IL-5, IL-6, IL-8, IL-17A, IL-33) in 80 asthmatics. A total of 17/80 patients were treated with biologics (10 with omalizumab, 7 with benralizumab). RESULTS: a total of 31% of patients had eosinophilic asthma (EA), 30% had mixed granulocytic asthma (MGA), 24% had paucigranulocytic asthma (PGA), and 15% had neutrophilic asthma (NA). The difference was found in blood eosinophils (p = 0.002), the highest observed in EA. The cut-off ≥ 240/µL eosinophils, with 64% sensitivity and 72.7% specificity, identified EA (AUC = 0.743, p = 0.001). A higher IL-8 level was associated with NA (p = 0.025). In 63 non-biologic asthma group, eosinophils were higher in EA than in NA, MGA, and PGA (p = 0.012, p = 0.028, and p = 0.049, respectively). A higher IL-17A was associated with EA without biologics (p = 0.004). A significantly higher IL-5 was found in EA treated with biologics, in comparison with EA without biologics (p = 0.043). The number of leucocytes and neutrophils was higher in MGA without biologics (p = 0.049, p = 0.019), while IL-5, IL-6, and IL-8 levels were higher in MGA treated with biologics (p = 0.012, p = 0.032, p = 0.038, respectively). CONCLUSIONS: EA and MGA were the most prevalent asthma phenotypes. Blood eosinophils can identify EA, both in patients with and without biologics. Apart from the clinical profile, a broad spectrum of biomarkers for assessing inflammatory phenotypes is necessary for an adequate therapy approach to patients with asthma.

Epstein-Barr virus infection as potential indicator of the occurrence and clinical presentation of systemic lupus erythematosus.

Introduction: The relationship between Systemic lupus erythematosus (SLE) and Epstein-Barr virus (EBV) infection has been suggested for decades, but the underlying mechanism of the EBV influence on SLE development remains to be elucidated. Methods: The goals of this research, which included 103 SLE patients and 99 controls, were to investigate the association of the parameters of EBV infection and SLE, to explore whether pooled demographic, clinical and EBV markers achieve a more significant effect on SLE development than each of them individually, and to evaluate EBV nuclear antigen 1 (EBNA1) and latent membrane protein 1 (LMP1) gene polymorphisms in isolates from SLE patients. Results: Comprehensive results related to serological, molecular and sequence markers of EBV infection in SLE patients demonstrated even 24 times higher possibility of having SLE if there is the presence of anti-EBV-EA(D) (early antigen) IgG antibodies (OR=24.086 95%CI OR=2.86-216.07, p=0.004). There was the same distribution of glucocorticoids (p=0.130), antimalarials (p=0.213), and immunosuppressives (p=0.712) in anti-EBV-EA(D) IgG positive and negative SLE patients. Further, higher anti-EBV-EA(D) IgG antibodies titers were identified as independent factors associated with lymphopenia, hematological SLE manifestation (OR=1.041, 95%CI OR=1.01-1.08, p=0.025, while a higher titer of anti-CA (viral capsid antigen) IgG antibodies (OR=1.015, 95%CI OR=1.01-1.03, p=0.019) and positive RF (rheumatoid factors) (OR=4.871, 95%CI OR=1.52-15.61, p=0.008) were identified as independent factors associated with alopecia within SLE. Finally, novel data on EBV EBNA1 and LMP1 gene polymorphisms in lupus are reported. Conclusion: The results support further investigation targeting EBV as a prognostic marker and therapeutic goal for lupus.

Myositis-specific autoantibodies in a non-traveler, patient from a non-endemic country, with Plasmodium vivax malaria.

INTRODUCTION: Autoantibodies (AAb) are a hallmark of immune-mediated inflammatory diseases. Malaria is a parasitic disease caused by Plasmodium protozoa. Individuals with malaria may present with a wide range of symptoms. It is frequently linked to the development of different AAb. CASE DESCRIPTION: A 35-year-old male presented with repeated episodes of fever, malaise, myalgia, dark urine, and yellowish sclera. Initial diagnostic workup revealed severe Coombs-positive anemia, increased C-reactive protein, and procalcitonin, pathological liver tests, high concentration of serum IgE, IgG, IgM, IgA, positive antinuclear antibodies (ANA), and positive antineutrophil cytoplasmatic antibodies (ANCA). In addition, myositis-specific antibodies directed to polymiositis-scleroderma 75 protein (PmScl75), threonyl-tRNA synthetase (PL-7), alanyl-tRNA synthetase (PL-12), Mi-2 antigen (Mi-2), Ku DNA helicase complex (Ku), signal recognition particle (SRP), and antiaminoacyl tRNA synthetase (EJ) were detected. The patient was suspected of having systemic lupus erythematosus and sent to the Clinic of Allergy and Immunology for further evaluation and treatment. A peripheral blood film examined by the hematologist during an episode of fever revealed intra-erythrocytic parasitic forms of Plasmodium vivax (P. vivax). After being diagnosed with P. vivax malaria, he was transferred to the Clinic for Infective and Tropical Diseases. The therapy consisted of artesunate/mefloquine and prednisone led to a complete clinical recovery and autoantibodies gradually disappeared. CONCLUSIONS: Malaria would not normally be considered during the initial diagnostic workup in a non-traveler and a patient from a non-endemic country. However, a thorough parasitic evaluation in patients presenting with a broad range of autoantibodies might be of particular importance.

Uncovering the Role of Epstein-Barr Virus Infection Markers for Remission in Rheumatoid Arthritis.

Epstein-Barr virus (EBV) infection has been shown as a potential risk factor for the development of rheumatoid arthritis (RA). This prospective research aimed to investigate whether EBV infection markers changed during the six-month follow-up period in 133 RA patients (80 newly diagnosed on methotrexate (MTX)-RA-A, and 53 on biologic therapy-RA-B) and whether it was related to a disease outcome. Reduction of disease activity and inflammation was obtained. A significant decline in seroprevalence and titer for anti-VCA-IgM (p = 0.022 and p = 0.026) and anti-EA(D)-IgM (p = 0.022 and p = 0.006) in RA-A, and in seroprevalence and titer of anti-EA(D)-IgG in the RA-B subgroup (p = 0.021 and p = 0.006) were detected after the follow-up. A lower titer of anti-EBNA1-IgG could be considered a significant marker of RA remission in all RA patients regardless of age and gender (OR = 0.99, 95% CI OR = 0.98-0.99, p = 0.038), and also in RA-B patients separately (OR = 0.988, 95% CI OR = 0.98-0.99, p = 0.041). This study supported the basic hypothesis that the immune response to EBV infection is involved in the RA pathogenesis, at the beginning of the disease or during the RA evolution. Moreover, the potential influence of MTX or TNF-alpha inhibitors on the impairment of the host to control EBV infection was indirectly refuted.

Markers of Epstein-Barr Virus Infection in Association with the Onset and Poor Control of Rheumatoid Arthritis: A Prospective Cohort Study.

Although the connection between Epstein-Barr virus (EBV) and rheumatoid arthritis (RA) has been studied for over 40 years, many questions still need clarification. The study aimed to analyze the possible association between anti-EBV antibody titers, EBV DNA viremia, EBV infection status and EBNA1 (Epstein-Barr nuclear antigen 1-EBNA1) variants and clinical parameters of RA patients. This prospective cohort study included 133 RA patients and 50 healthy controls. Active/recent EBV infection was more prevalent in RA patients than in controls (42% vs. 16%, p < 0.001). RA patients had higher titers of anti-EBV-CA-IgM (capsid antigen-CA) and anti-EBV-EA(D)-IgG (early antigen-EA) antibodies than controls (p = 0.003 and p = 0.023, respectively). Lower levels of anti-EBNA1-IgG and anti-EBV-CA-IgG were observed in RA patients who received methotrexate (anti-EBNA1 IgG p < 0.001; anti-EBV-CA IgG p < 0.001). Based on amino acid residue on position 487, two EBNA1 prototypes were detected: P-Thr and P-Ala. Patients with active/recent EBV infection had a five times more chance of having RA and a nearly six times more chance of getting RA. Also, EBV active/recent infection is twice more likely in newly diagnosed than in methotrexate-treated patients. Further studies are needed to clarify "who is the chicken and who is the egg" in this EBV-RA relationship.

Association of IL10RA, IL10RB, and IL22RA Polymorphisms/Haplotypes with Susceptibility to and Clinical Manifestations of SLE.

Systemic lupus erythematosus (SLE) is characterized by an imbalance between proinflammatory and anti-inflammatory mediators. Single-nucleotide polymorphisms (SNPs) in genes coding IL10RA, IL10RB, and IL22RA could affect their expression or function and disrupt immune homeostasis. We aimed to analyze the associations of IL10RA, IL10RB, and IL22RA polymorphisms/haplotypes with patients' susceptibility to and clinical manifestations of SLE. Our study included 103 SLE patients and 99 healthy controls. The genotypes of the selected polymorphisms within IL10RA (rs10892202, rs4252270, rs3135932, rs2228055, rs2229113, and rs9610), IL10RB (rs999788, rs2834167, and rs1058867), and IL22RA (rs3795299 and rs16829204) genes were determined by TaqMan® Assays. IL10RB rs1058867 G allele carriers were significantly more frequent among the controls than among the SLE patients (76.8% vs. 61.2%; p = 0.017, OR = 0.477, 95% CI: 0.258-0.879). The IL10RB CAA haplotype was more frequent among the SLE patients than in the control group (42.7% vs. 30.7%; p = 0.027). The IL22RA rs3795299 C allele and rs16829204 CC genotype were associated with Hashimoto thyroiditis in the SLE patients (n = 103; p = 0.002 and p = 0.026, respectively), and in all the included participants (n = 202, p < 0.000 and p = 0.007, respectively), and the IL22RA CC haplotype was more frequent in the SLE patients with Hashimoto thyroiditis (p = 0.047) and in the overall participants with Hashimoto thyroiditis (n = 32, p = 0.004). The IL10RA, IL10RB, and IL22RA polymorphisms/haplotypes could be associated with SLE susceptibility and various clinical manifestations, and the IL22RA CC haplotype could be associated with Hashimoto thyroiditis.

Autoimmune/inflammatory syndrome induced by adjuvants in a woman with Hashimoto thyroiditis and familial autoimmunity-a case report and literature review.

Introduction: Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) consists of a wide spectrum of symptoms and immunological features that are believed to develop in predisposed individuals after exposure to an adjuvant, including a silicone breast implant (SBI). Different autoimmune diseases (AIDs) have been associated with ASIA, but ASIA development after SBI in women with Hashimoto thyroiditis (HT) and familial autoimmunity has rarely been described. Case report: A 37-year-old woman presented in 2019 with arthralgia, sicca symptoms, fatigue, + antinuclear antibody (ANA), + anti SSA, and + anticardiolipin Immunoglobulin G (IgG) antibodies. She was diagnosed with HT and vitamin D deficiency in 2012. The familial autoimmunity was present: the patient's mother had been diagnosed with systemic lupus erythematosus and secondary Sjogren's syndrome and her grandmother with cutaneous lupus and pernicious anemia. In 2017, the patient had a cosmetic SBI procedure that was complicated by repeated right breast capsulitis. After 2 years of irregular visits due to COVID-19, she presented with + ANA, + anticentromere antibodies both in sera and seroma, sicca syndrome, arthralgias, twinkling in extremities, abnormal capillaroscopic findings, and reduced diffusing capacity of the lungs for carbon monoxide. She was diagnosed with ASIA, and antimalarial and corticosteroid therapy were introduced. Conclusion: In patients with HT and familial autoimmunity, SBI should be carefully considered due to the possibility of ASIA development. Hashimoto thyroiditis, familial autoimmunity, and ASIA seem to be interconnected in the complex mosaic of autoimmunity in predisposed individuals.

Epstein-Barr Virus Reactivation as a New Predictor of Achieving Remission or Lupus Low Disease Activity State in Patients with Systemic Lupus Erythematosus with Cutaneous Involvement.

Although Epstein-Barr virus (EBV) reactivation has long been associated with the pathogenesis of systemic lupus erythematosus (SLE), many aspects of this relationship remain unclear. Our objective was to investigate the association between EBV reactivation and the achievement of SLE remission and lupus low disease activity state (LLDAS) over a six-month period. Clinical, laboratory, and virological tests (anti-EBV antibodies and EBV DNA) were performed among 51 patients with the active form of SLE on two occasions six months apart. SLE remission and LLDAS achievement were assessed at the end of the follow-up period. Active EBV infection was detected in 45% of active SLE patients at baseline, and 77% transitioned to latent EBV infection at six months (p < 0.001). Multivariate regression revealed a higher titer of anti-EA(D) IgM-Abs and the presence of anti-EA(D) IgM-Abs as independent predictors of remission and LLDAS in SLE patients with mucocutaneous manifestations (p = 0.042) and rash only (p = 0.023), respectively. Since a higher C3 level was an independent predictor of transition to latent EBV infection (p = 0.027), the estimated cut-off value that could identify active SLE patients who will transition to latent EBV infection after six months was ≥0.780 g/L with a sensitivity of 70.6% and a specificity of 75.0% (AUC = 0.756, p = 0.003). EBV reactivation is common in patients with active SLE, and most of them transition to latent EBV infection after six months. Achieving remission and LLDAS in SLE patients with mucocutaneous manifestations can be predicted by a higher titer, whereas in SLE patients who have only a rash, the presence of anti-EA (D) IgM-Abs was a predictor of remission and LLDAS.

Large-Vessel Giant Cell Arteritis following COVID-19-What Can HLA Typing Reveal?

Giant cell arteritis (GCA) is an immune-mediated vasculitis that affects large arteries. It has been hypothesized that viruses may trigger inflammation within the vessel walls. Genetic studies on human leukocyte antigens (HLAs) have previously reported HLA-DRB1*04 as a susceptible allele for GCA and HLA-DRB1*15 as a protective allele for GCA. Here, we discuss the clinical presentation, laboratory findings, HLA class I and class II analysis results, and management of patients with extracranial large-vessel (LV) GCA, detected at least six weeks after recovery from COVID-19. This case series encompassed three patients with LV-GCA (two males and a female with an age range of 63-69 years) whose leading clinical presentation included the presence of constitutional symptoms and significantly elevated inflammatory markers. The diagnosis of LV-GCA was confirmed by CT angiography and FDG-PET/CT, revealing inflammation in the large vessels. All were treated with corticosteroids, while two received adjunctive therapy. By analyzing HLA profiles, we found no presence of the susceptible HLA-DRB1*04 allele, while the HLA-DRB1*15 allele was detected in two patients. In conclusion, LV-GCA may be triggered by COVID-19. We highlight the importance of the early identification of LV-GCA following SARS-CoV-2 infection, which may be delayed due to the overlapping clinical features of GCA and COVID-19. The prompt initiation of therapy is necessary in order to avoid severe vascular complications. Future studies will better define the role of specific HLA alleles in patients who developed GCA following COVID-19.

Autoimmune and immunoserological markers of COVID-19 pneumonia: Can they help in the assessment of disease severity.

Background: Immune dysregulation and associated inefficient anti-viral immunity during Coronavirus Disease 2019 (COVID-19) can cause tissue and organ damage which shares many similarities with pathogenetic processes in systemic autoimmune diseases. In this study, we investigate wide range autoimmune and immunoserological markers in hospitalized patients with COVID-19. Methods: Study included 51 patients with confirmed Severe Acute Respiratory Syndrome Coronavirus 2 infection and hospitalized due to COVID-19 pneumonia. Wide spectrum autoantibodies associated with different autoimmune inflammatory rheumatic diseases were analyzed and correlated with clinical and laboratory features and pneumonia severity. Results: Antinuclear antibodies (ANA) positivity was found in 19.6%, anti-cardiolipin IgG antibodies (aCL IgG) in 15.7%, and anti-cardiolipin IgM antibodies (aCL IgM) in 7.8% of patients. Positive atypical x anti-neutrophil cytoplasmic antibodies (xANCA) were detected in 10.0% (all negative for Proteinase 3 and Myeloperoxidase) and rheumatoid factor was found in 8.2% of patients. None of tested autoantibodies were associated with disease or pneumonia severity, except for aCL IgG being significantly associated with higher pneumonia severity index (p = 0.036). Patients with reduced total serum IgG were more likely to require non-invasive mechanical ventilation (NIMV) (p < 0.0001). Serum concentrations of IgG (p = 0.003) and IgA (p = 0.032) were significantly lower in this group of patients. Higher total serum IgA (p = 0.009) was associated with mortality, with no difference in serum IgG (p = 0.115) or IgM (p = 0.175). Lethal outcome was associated with lower complement C4 (p = 0.013), while there was no difference in complement C3 concentration (p = 0.135). Conclusion: Increased autoimmune responses are present in moderate and severe COVID-19. Severe pneumonia is associated with the presence of aCL IgG, suggesting their role in disease pathogenesis. Evaluation of serum immunoglobulins and complement concentration could help assess the risk of non-invasive mechanical ventilation NIMV and poor outcome.

Comprehensive Analysis of the HLA Class I and the HLA Class II Alleles in Patients with Takayasu Arteritis: Relationship with Clinical Patterns and Prognosis

BACKGROUND: Takayasu arteritis (TA) is a systemic vasculitis, affecting mainly the aorta and its branches. OBJECTIVE: To analyze the HLA class I and class II alleles in patients with TA and explore their relationship with clinical and demographic characteristics, and potential significance in prognosis. METHODS: Twenty-five, unrelated TA patients were genotyped for HLA-A, HLA-B, HLA-C, HLA-DRB1, and the HLA-DQB1 loci. The frequencies of the HLA-A, HLA-B, and the HLA-DRB1 were compared with a control group of 1992, while the HLA-C and the HLA-DQB1 were compared with a group of 159 healthy, unrelated individuals. RESULTS: Among TA patients, 5/25 (20%) were identified as the HLA-B*52 carriers. There was a significant difference in the HLA-B*52 allele frequency in the TA patients (10%) compared with the healthy controls (1.2%). Moreover, presence of the HLA-B*52 was associated with significantly earlier disease onset, more severe clinical presentations, and a poorer response to treatment. The HLA-C*03 was detected in 32% of patients and was present exclusively in those with a clinically mild form of the TA, indicating a putative protective effect. CONCLUSION: These findings indicate that the HLA-B*52 allele contributes to a higher susceptibility to the TA whereas the HLA-C*03, can be a protective factor in the TA.

Enhanced Liver Fibrosis Score as a Biomarker for Vascular Damage Assessment in Patients with Takayasu Arteritis-A Pilot Study.

Takayasu Arteritis (TA) is characterized by granulomatous panarteritis, vessel wall fibrosis, and irreversible vascular impairment. The aim of this study is to explore the usefulness of the Enhanced Liver Fibrosis score (ELF), procollagen-III aminoterminal propeptide (PIIINP), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and hyaluronic acid (HA) in assessing vascular damage in TA patients. ELF, PIIINP, TIMP-1, and HA were measured in 24 TA patients, and the results were correlated with the clinical damage indexes (VDI and TADS), an imaging damage score (CARDS), and disease activity scores (NIH and ITAS2010). A mean ELF score 8.42 (±1.12) and values higher than 7.7 (cut-off for liver fibrosis) in 21/24 (87.5%) of patients were detected. The VDI and TADS correlated significantly to ELF (p < 0.01). Additionally, a strong association across ELF and CARDS (p < 0.0001), PIIINP and CARDS (p < 0.001), and HA and CARDS (p < 0.001) was observed. No correlations of the tested biomarkers with inflammatory parameters, NIH, and ITAS2010 scores were found. To our knowledge, this is the first study that suggests the association of the serum biomarkers PIIINP, HA, and ELF score with damage but not with disease activity in TA patients. The ELF score and PIIINP may be useful biomarkers reflecting an ongoing fibrotic process and quantifying vascular damage.

Biomarkers of disease activity in patients with chronic spontaneous urticaria.

INTRODUCTION: Previous studies have examined biomarkers of coagulation, inflammation and immunity in chronic spontaneous urticaria (CSU), but no recommended biomarkers for disease activity have been established yet. AIM: To find the relationship between certain laboratory parameters and disease activity in patients with CSU. MATERIAL AND METHODS: Serum concentrations of D-dimer, C-reactive protein (CRP), C3, C4, and prothrombin time (PT), activated partial thromboplastin time (aPTT) values were measured in 44 CSU patients and compared with 33 healthy controls. Correlation between biomarkers and urticaria activity score during 7 consecutive days (UAS7) was calculated. RESULTS: Our study included 44 CSU patients (38 females and 6 males), mean age of 50.4 years and the average disease duration of 3.1 years. Based on UAS7, 23 (52.3%) CSU patients had mild urticaria, 8 (18.2%) well-controlled, 7 (15.9%) moderate and 6 (13.6%) severe urticaria. Fourteen (31.8%) patients had elevated CRP, 21 (47.7%) had elevated D-dimer and 14 (13.6%) CSU patients had elevated C4 levels. Patients with CSU had statistically significant elevated D-dimer, CRP and PT as compared with controls (p = 0.007, p = 0.005 and p = 0.029, respectively). There was no correlation between PT, aPTT, D-dimer, CRP, C3 and disease activity. Statistically significant differences in C4 levels between patients with severe and well-controlled, mild, moderate urticaria were determined (p = 0.003). CONCLUSIONS: CRP, D-dimer, and PT may be considered as biomarkers for distinguishing patients with CSU from controls. The C4 levels correlate with disease activity and may be useful as a potential biomarker of disease activity.

Severe strongyloidiasis and systemic vasculitis: comorbidity, association or both? Case-based review.

A possible association between strongyloidiasis and systemic vasculitis is rarely reported in the literature. We report the case of a patient with severe strongyloidiasis and an angiographic finding consistent with polyarteritis nodosa. Diagnosis of strongyloidiasis was made by finding of larvae and adult parasites in samples of the upper gastrointestinal tract mucosa and stool. The patient was treated with albendazole, ivermectin and corticosteroid withdrawal. This therapy led to the resolution of symptoms, with repeated stool samples negative for S. stercoralis. However, the clinical course was complicated with pulmonary tuberculosis. Despite tuberculostatic therapy and supportive measures, a lethal outcome occurred. The report is followed by a focused review of the available literature on the association of strongyloidiasis and systemic vasculitis.

CLINICAL CHARACTERISTICS AND TREATMENT OF MELKERSSON-ROSENTHAL SYNDROME--OVERVIEW OF SIX PATIENTS.

INTRODUCTION: Melkersson-Rosenthal syndrome is a rare disease of unknown etiology. Histopathologically, it presents as granulomatous cheilitis. From laboratory aspect, it is a nonspecific, differential diagnostically and therapeutically complex condition. CASE REPORT: This is a report of six cases treated at the Department of Allergology and Immunology of the Clinical Center of Serbia, who had presented with the referral diagnosis of recurring or persistent lip edema, and who were diagnosed with Melkersson-Rosenthal syndrome upon detailed evaluation. Three patients had complete triad of symptoms, two had the oligosymptomatic form and one manifested the monosymptomatic form of the disease. Histopathological findings of the oral mucosa specimens verified the presence of non-necrotic epithelioid granulomas in all patients. The patients were treated with the H1 and H2 antihistamines, corticosteroids, followed by anabolic drugs and antibiotics, resulting in transient and unfavorable effects. CONCLUSION: In differential diagnosis, Melkersson-Rosenthal syndrome diagnosis primarily refers to conditions of angioneurotic edema and hereditary angioedema, as well as granulomatous diseases such as sarcoidosis, tuberculosis and Chron's disease. It is necessary to follow-up these patients in view of monitoring the effects of the therapy and possible development of systemic granulomatous diseases.

Vitamin D Status in Patients with Systemic Lupus Erythematosus in Serbia: Correlation with Disease Activity and Clinical Manifestations.

BACKGROUND: Numerous studies indicate potential role of vitamin D as an important factor in the development of many autoimmune diseases including systemic lupus erythematosus (SLE). Patients with SLE are especially prone to the development of vitamin D deficiency due to the nature of their illness. AIM: The aims of our study were to determine the prevalence of vitamin D insufficiency and deficiency in patients with SLE in Serbia, to identify clinical variables associated with vitamin D status and to examine the impact of vitamin D status on disease activity and presence of specific lupus autoantibodies. MATERIAL AND METHODS: The study included 46 patients with SLE. Serum 25(OH)D concentration was measured by electrohemiluminiscent immunoassay. RESULTS: The mean serum concentration of 25(OH)D was 11.9 ± 7.3 ng/ml. The prevalence of insufficiency was 32.6%, while the prevalence of deficiency was 67.4%. There was no association between vitamin D status and photosensitivity, skin lesions, arthritis and lupus nephritis. Vitamin D status was not associated with the presence of specific autoantibodies. There was no correlation between disease activity assessed by SLEDAI scale with the concentration of 25(OH)D. Patients who used vitamin D supplements and calcium did not have a significantly higher concentration of 25(OH)D. CONCLUSION: In conclusion, vitamin D deficiency is common in patients with SLE.

Sjögren's Syndrome and Silicosis - a Case Report.

Sjögren's syndrome is an autoimmune disease of unknown etiology where immune response to self-antigens is believed to result from interactions between genetic and environmental factors. We describe the case of a patient who has been diagnosed with Sjögren's syndrome based on typical clinical and immunological parameters. The clinical picture was dominated by the respiratory symptoms, and radiographic and multislice computed tomography examination of the chest showed certain changes characteristic of pneumoconiosis. Given that the patient has worked in a foundry where he has been exposed to the silica dust, he was subject to examination by occupational health specialists under the suspicion of lung silicosis, who confirmed the silicosis. This case report points to the possible connection between a professional exposure to silica and Sjögren's syndrome. Occupational exposure to silica is a possible risk factor for the development of autoimmune diseases, and in the evaluation of patients with connective tissue diseases it is important to consider work-related history.