Refractory systemic lupus erythematosus with chylous effusion successfully treated with sirolimus: a case report and literature review.

Chylous effusion is a rare manifestation of systemic lupus erythematosus (SLE). When it does occur in SLE, it is generally well treated with standard pharmacologic or surgical measures. We present a decade of management in a case of SLE with lung affliction and development of refractory bilateral chylous effusion and pulmonary arterial hypertension (PAH). In the first years, the patient was treated under a Sjogren syndrome diagnose. After few years, her respiratory condition worsened due to chylous effusion and PAH. Immunosuppression therapy (methylprednisolone) was reintroduced, and vasodilator therapy commenced. With this, her cardiac function remained stable, but respiratory function continuously worsened despite several therapy trials with different combinations of immunosuppressant (glucocorticoids, resochin, cyclophosphamide and mycophenolate mofetil). On top of pleural effusion worsening, the patient developed ascites and severe hypoalbuminaemia. Even though albumin loss was stabilized with monthly octreotide applications, the patient remained respiratory insufficient and in need of continuous oxygen therapy. At that point, we decided to introduce sirolimus on top of glucocorticoids and mycophenolate mofetil therapy. Her clinical status, radiological finding, and lung function gradually improved and she became respiratory sufficient at rest. The patient remains in our follow-up and has been stable on given therapy for over 3 years despite overcoming a severe COVID-19 pneumonia in 2021. This case adds to the body of evidence of sirolimus effectiveness in patients with refractory systemic lupus and is, to our best knowledge, the first case to report its successful application in a patient with SLE and refractory chylous effusion.

Rituximab as a treatment option in a patient with rheumatoid arthritis and a history of malignancy-intracranial chondrosarcoma/osteochondroma-case based review.

When compared to general population, patients with rheumatoid arthritis are at higher risk of some malignancies (especially lymphomas and lung cancer). Genetic predisposition, chronic inflammatory stimuli and viral infections are some of the reasons untreated patients are at higher risk. Clinical studies and national/international registries collect the data about the malignancies with higher incidence (such as lung, skin and breast cancer) but on the other hand, malignancies with lower incidence (such as sarcomas) are rarely reported. We report a case of a 47-year-old male with a history of a malignant intracranial chondrosarcoma/osteochondroma who developed seropositive rheumatoid arthritis. Due to progression of erosions, the patient was initialy treated with conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) and later on with rituximab. The patient's rheumatoid arthritis went and remained in remission on maintenance therapy with rituximab (every 6-8 months) and low-dose methotrexate with no relapse of malignant intracranial chondrosarcoma/osteochondroma. Rituximab should be considered as a treatment option in patients with rare and agressive malignancies, such as sarcomas.

Guidelines for the prevention, detection and therapy of vitamin d deficiency in adults

It is estimated that over one billion of people around the globe have low serum values of vitamin D, therefore, we can consider vitamin D deficiency as a pandemic and public health problem. Geographic position of Croatia, especially the continental part of the country, is a risk factor for the development of deficiency of vitamin D in the population. The aim of these guidelines is to provide the clinicians with easy and comprehensive tool for prevention, detection and therapy of vitamin D deficienney in healthy population and various groups of patients. They were made as a result of collaboration of clinicians of different backgrounds who are dealing with patients at risk of vitamin D deficiency. These guidelines are evi- dence-based, according to GRADE-system (Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendation. The main conclusions address the recommended serum vitamin D values in the population which should be between 75 and 125 nmol/L and defining recommended preven- tive and therapeutic dosages of vitamin D in order to reach the adequate levels of serum vitamin

Influence of dose-death interval on colchicine and metabolite distribution in decomposed skeletal tissues.

The semi-quantitative analysis of decomposed bone of rats exposed to colchicine and euthanized following different time intervals postexposure (i.e., dose-death interval, DDI) is described. Rats received colchicine (50 mg/kg, i.p.) and were euthanized 30 min (DDI1; n = 4), 60 min (DDI2; n = 4), or 180 min (DDI3; n = 4) postdose. Drug-free animals (n = 3) served as negative controls. Perimortem heart plasma was collected. Remains were decomposed to skeleton outdoors and then collected and sorted (skull, vertebrae, rib, pelvis, femur, tibia). Bones were dried, pulverized, and prepared by microwave-assisted extraction and microplate solid-phase extraction (MAE-MPSPE), followed by analysis for colchicine, 3-demethylcolchicine (3DMC), and 2-demethylcolchicine (2DMC) by ultra-high-performance liquid chromatography with photodiode array detection (UHPLC-PDA) at 350 nm. Bone type was a main effect (Kruskall-Wallis, p < 0.05) with respect to drug level (expressed as mass-normalized response ratio, RR/m) for each analyte, at each DDI. For all samples, DDI was a main effect (Kruskall-Wallis, p < 0.05) with respect to analyte level, and the ratio of analyte levels (RR3DMC/RRCOLCH, RR2DMC/RRCOLCH, and RR2DMC/RR3DMC). Bone COLCH levels varied by 19-fold, 12-fold, and 60-fold across all bone types in the DDI1, DDI2, and DDI3 groups, respectively. Bone 3DMC levels varied by 12-fold, 11-fold and 17-fold across all bone types in the DDI1, DDI2, and DDI3 groups, respectively. Bone 2DMC levels varied by 20-fold, 14-fold, and 14-fold across all bone types in the DDI1, DDI2, and DDI3 groups, respectively. Values of RR3DMC/RRCOLCH varied by 16-fold, 5-fold, and 5-fold across all bone types in the DDI1, DDI2, and DDI3 groups, respectively. Values of RR2DMC/RRCOLCH varied by 10-fold, 6-fold, and 12-fold across all bone types in the DDI1, DDI2, and DDI3 groups, respectively. Values of RR2DMC/RR3DMC varied by 3-fold, 5-fold, and 2-fold across all bone types in the DDI1, DDI2, and DDI3 groups, respectively. Measured analyte levels in bone correlated poorly with corresponding levels in blood (r = -0.65-+0.31). Measured values of RR2DMC/RRCOLCH and RR2DMC/RR3DMC in bone also correlated poorly with corresponding values in blood. Measured values of RR3DMC/RRCOLCH were well correlated with corresponding blood levels for all bone types except skull (r = 0.91-0.97).

Solitary pulmonary amyloidoma mimicking lung cancer on 18F-FDG PET-CT scan in systemic lupus erythematosus patient.

Localized amyloid deposits (tumoral amyloidosis or amyloidoma) are uncommon form of amyloidosis and nodular pulmonary amyloidomas are rarely found. This incidental finding can mimic a bronchopulmonary neoplasm and may occur secondarily to an infectious, inflammatory or lymphoproliferative disease. We report a case of a 62-year-old female with long-standing systemic lupus erythematosus (SLE) with low compliance who presented with radiologically-verified solitary pulmonary nodule. Work-up included positron emission tomography-computed tomography (PET-CT) scan, which revealed hypermetabolic uptake of (18)F-fluorodeoxyglucose, and lobectomy was performed. Staining of the tissue was positive for Congo red and was green birefringent under polarized light. Immunohistochemical methods excluded lymphoproliferative disease and confirmed amyloidoma. SLE was controlled with antimalarials and glucocorticoids. Pulmonary amyloidoma should be considered in the differential diagnosis of solitary lung nodules.

Catastrophic antiphospholipid syndrome associated with systemic lupus erythematosus treated with rituximab: case report and a review of the literature.

Catastrophic antiphospholipid syndrome (CAPS) is a rare, acute, life-threatening form of antiphospholipid syndrome. In the last several decades there has been a significant improvement in the treatment of patients with CAPS, but the overall mortality is still very significant. The use of rituximab has been reported in the treatment of refractory cases of CAPS but the data are still scarce and inconclusive. We report a case of 47-year old male patient with long standing SLE and secondary APS who presented with acute thromboembolic incident (partial thrombosis of superior mesenteric artery). During the first week of his hospitalization he met the criteria for probable CAPS. He was treated with anticoagulants, glucocorticoids, intravenous immunoglobulins and systemic antibiotics. Finally he was treated with rituximab. There was no response to the implemented treatment and he eventually died. Autopsy showed evidence of small vessel thrombosis in the lung microvasculature. With this the criteria for definitive CAPS were fulfilled. To our knowledge, at present time, this is the first ever reported case of definitive CAPS associated with SLE treated with rituximab. There is a great need for further investigation to evaluate the effectiveness of rituximab in treatment of CAPS.

Pregnancy-related severe pelvic girdle pain caused by unilateral noninfectious sacroiliitis. A case report and literature review.

Pelvic girdle pain during and after pregnancy is the clinical syndrome of persistent musculoskeletal pain localized in the posterior and/or anterior aspect of the pelvis originating from sacroiliac joints and/or pubic symphysis due to dynamic instability. We report the case of severe and disabling postpartum pelvic girdle pain caused by unilateral noninfectious sacroiliitis which resolved after 2 months by nonsteroidal anti-inflammatory drug and physical therapy. A short literature review is given on epidemiology, etiology, clinical presentation, therapy, and prognosis of pregnancy-related pelvic girdle pain.

Effects of dopaminergic drugs on inflammatory bowel disease induced with 2,4-dinitrofluorbenzene in BALB/c mice.

The aim of the study was to demonstrate the effects of dopaminergic drugs on 2,4-dinitrofluorbenzene (DNFB) induced experimental inflammatory bowel disease (IBD) in previously sensitized BALB/c mice. The number and extent of ulcerations and erosions, the intensity of haemorrhages, oedema, and accumulation of neutrophils and eosinophils within colonic lamina propria and submucosa were scored and statistically evaluated. The 180 BALB/c mice, were allocated into three equal groups. The mice in the first experimental group were treated with domperidone (DP), a peripheral dopamine (DA) antagonist. The mice from the second experimental group were treated with bromocriptine (BC), a dopamine agonist. The mice from the control group were treated with an equivalent volume of normal saline in the same manner. Ten animals from each group were killed on days 1, 2, 3, 5 and 10, subsequent to the challenge enema of DNFB solution. Gross and microscopic examination of the colon was performed. Treatment with BC resulted in clinical improvement and decreased mortality rate by 2 of 60 (3%), while domperidone treatment increased mortality rate to 12 of 60 (20%) compared with the controls [4 of 60 (6%)]. The analysis of the microscopic lesions indicated that the beneficial effects of BC were the result of maintenance of vascular integrity.

Systemic lupus erythematosus. Disease outcome in patients with a disease duration of at least 10 years: second evaluation.

Data related to the disease course of patients with systemic lupus erythematosus (SLE) with special attention to the persistence of disease activity in the long term are scarce. At this moment reliable figures are only known about the survival rate as a measure of outcome. The aim of this multicenter study was to describe the outcome of SLE patients with a disease duration of greater than 10 y. Outcome parameters were two disease activity-scoring systems (SLEDAI and ECLAM), the end organ damage (SLICC/ACR damage index) and treatment. Our results are derived from 187 SLE patients followed at 10 different centres in Europe over a period of 1 y. Serious clinical signs or exacerbations, defined by the occurrence or detoriation of already existing symptoms of renal and cerebral nervous systems were observed in 2-11% of the patients, seizures and psychosis in 3%, proteinuria in 11% and an increase in serum creatinine in 5% of the patients. No change took place in the overall damage index. Yet, the disease course in most patients was characterized by periods of tiredness (42-60%), arthritis (20-25%), skin involvement such as malar rash (32-40%), migraine (15-20%), anaemia (15%) and leucopenia (17-19%). Summarizing these results it is shown that patients, still under care after such a long time of having this disease, do have a disease that is far from extinguished.

Incomplete lupus erythematosus: results of a multicentre study under the supervision of the EULAR Standing Committee on International Clinical Studies Including Therapeutic Trials (ESCISIT).

OBJECTIVE: Patients characterized with antinuclear antibodies (ANA) and disease symptoms related to one organ system can be described as having incomplete systemic lupus erythematosus (SLE). The aim of this multicentre study was to describe the outcome of these so-called incomplete SLE patients. Two aspects of the outcome were studied: (i) the disease course, defined by the presence or absence of clinical symptoms; and (ii) the number of patients that eventually developed full SLE. METHODS: Outcome parameters were the ACR criteria, the SLE disease Activity Index (SLEDAI), the European Consensus Lupus Activity Measure (ECLAM) and the requirement for treatment. In 10 European rheumatology centres, patients who had been evaluated in the last 3 months of 1994 and had been diagnosed as having incomplete SLE on clinical grounds for at least 1 yr were included in the study. All 122 patients who were included in the study were evaluated annually during 3 yr of follow-up. RESULTS: Our results are confined to a patient cohort defined by disease duration of at least 1 yr, being under clinical care at the different centres in Europe. These patients showed disease activity that was related mostly to symptoms of the skin and the musculoskeletal system, and leucocytopenia. During the follow-up, low doses of prednisolone were still being prescribed in 43% of the patients. On recruitment to the study, 22 of the 122 incomplete SLE patients already fulfilled the ACR criteria for the diagnosis of SLE. In the 3 yr of follow-up only three patients developed SLE. CONCLUSIONS: A high proportion of patients in our cohort defined on clinical grounds as having incomplete SLE eventually showed disease activity defined by the SLEDAI as well as ECLAM. However, only three cases developed to SLE during the follow-up. This suggests that incomplete SLE forms a subgroup of SLE that has a good prognosis.

[Idiopathic eosinophilia with ascites (case report)]. / Idiopatska eozinofilija s ascitesom (prikaz bolesnika).

Hypereosinophilia can present a diagnostic problem if initial diagnostic procedures (medical history, physical examination and basic laboratory exams) fail to reveal the cause. Persistent finding of hypereosinophilia in such patients demands diagnostic intervention in order to rule out neoplastic and lymphoproliferative diseases, chronic inflammatory diseases of respiratory and gastrointestinal system and skin, and other inflammatory and postinflammatory conditions. If these disorders are ruled out, consideration should also be given to the diagnosis of primary hypereosinophilia, including idiopathic hypereosinophilic syndrome. The paper presents a patient with significant elevation of absolute and relative numbers of eosinophils in whom the only physical pathologic finding was eosinophilic ascites. Extensive diagnostic investigation did not prove secondary character of abnormalities, and since all pathologic findings receded during 7-month observation without treatment, the conclusion was that the disorder was benign.

[Methemoglobinemia caused by accidental poisoning with metolachlor and metobromuron]. / Methemoglobinemija uzrokovana akcidentalnom intoksikacijom metolaklorom i metobromuronom.

An 81-year-old man was admitted in the emergency department approximately four hours after accidental, ingestion of an unknown quantity of herbicide "Galex 500 EC". This product contains 25% of metolachlor and 25% of metobromuron dissolved in xylene. In spite of the fact that the combination of aniline and urea-substituted derivatives is widely used in agriculture as herbicide, there are very few data available about their harmful effects on humans. These agents appear to be mildly toxic, and rarely has a major systemic effect been reported after the poisoning. On admittance, our patient showed remarkable cyanosis and his methaemoglobin level was 38.4% of the total haemoglobin, rising next day to 46.2%. Only mild transient signs of hypoxic effects on central nervous system were observed and the laboratory findings indicated mild haemolysis. Methylene blue was applied intravenously in a dose of 1.5 mg/kg (10 ml, 1% solution) on the second day of admission. Administration of methylene blue was very effective and the patient was discharged from the hospital fully recovered.

[Intermittent intravenous cyclophosphamide application in patients with systemic lupus erythematosus]. / Intermitentna intravenska primjena ciklofosfamida u bolesnika sa sustavnim eritemskim lupusom.

The aim of this paper is retrospective analysis of data from patients in whom the indication for cyclophosphamide (CF) pulse therapy was established in our department. Indications for CF pulse treatment were lupus nephritis (LN) alone or associated with central nervous system lupus. CF was administred in the dose of 500-1000 mg/m2 intravenously once monthly for the 6 months and once every 3 months thereafter. Patients were treated with adequate dose of glucocorticoids and other symptomatic therapy. The effect of applied therapy has been analysed by monitoring proteinuria, serum creatinine concentration, creatinine clearance, ESR, ANF titer and total complement hemolytic activity. Initial therapeutic procedure has been completed in 25/30 patients. The reasons for discontinuation in 5/30 patients were as follows: end-stage renal failure in spite of therapy (1), psychosis and lost of compliance (1), recurrent pancytopenia and subsequent sepsis (1), death non related to SLE (1) and failure to show at follow-up (1). Significant improvement of all control parameters was observed in the majority of patients in whom the therapy was completely conducted. 16/25 patients continued therapy for the next 18 months and in only 1/16 patients therapy was discontinued because of end-stage renal failure. In other 15/16 patients further improvement of control parameters was observed, although not so expressed as in the first 6 months. The most frequent complications were infections (16 infections were microbiologically proved and there were probably more infections). Alopecia (2), haematuria (1) and amenorrhoea (1) were also observed. Relatively low incidence of complications may be explained by careful patient monitoring. Considering that therapeutic success is defined not only by the improvement of renal function, but by stopping of further progression of renal failure, it can be concluded that intermittent CF pulse therapy showed good effect on LN in patients with clear indication.

[The Budd-Chiari syndrome--case report of a patient with hepatic vein occlusion and adenocarcinoma of the lung]. / Budd-Chiarijev sindrom--prikaz bolesnika s okluzijom hepatalnih vena i adenokarcinomom pluca.

The case of a patient with sudden onset of abdominal pain, hepatomegaly and laboratory findings which indicated necrosis of a parenchymal organ is reported. Patient died soon after the admission to hospital after fulminant disease development. At the time of admission diagnosis of hepatic vein occlusion, i.e., Budd-Chiari syndrome was made based on ultrasonographic finding. Obduction confirmed this finding showing lung adenocarcinoma with liver metastases as well as occlusion of all hepatic vein branches with thrombi. This report emphasizes the role of ultrasonographic diagnostics in the early diagnosis of Budd-Chiari syndrome.

Histopathologic features of T-cell mediated colonic injury induced with 2,4-dinitrofluorobenzene in BALB/c mice.

The aim of the study was to reveal the histopathologic features of intestinal inflammation as demonstrated in BALB/c mice, using the challenge of 2,4-dinitrofluorobenzene (DNFB) with or without previous sensitization. Forty mice were randomized into 5 groups. Two groups of animals were treated with rectal enema of 0.2% or 1.0% of 2,4-dinitrofluorobenzene solution. Third group was pretreated with 2 sensitizing doses of DNFB. Two control groups were treated with PBS or acetone and vehicle enema only (acetone and olive oil). In order to assess the extent of colonic inflammation and damage, a histopathologic score scale was developed. In contrast to scanty superficial ulcerations and mild edema observed in the control group of animals, edema, ulcerations, hemorrhage, necrosis and infiltration of inflammatory cells were observed in experiment groups treated with enema of DNFB. Total score of lesion as well almost all inflammatory parameters of injury observed were highest in previously sensitized animals. The results of this study clearly demonstrated the pattern of colonic inflammation induced with DNFB using the histopathologic scoring scale system.

Animal models of inflammatory bowel disease.

The aim of this article was to reveal the major biologic features of intestine that predispose the intestinal mucosa to numerous inflammatory conditions, especially in regard to experimental models of inflammatory bowel disease. The need for the greater understanding of the etiology of intestinal inflammation and the search for more effective and novel therapy for the treatment of the disease has led to the development of variety of experimental models of inflammatory bowel disease. There is a growing number of animal models of inflammatory bowel disease, either naturally occurring in several mammalian species or inducible in various species of experimental animals by using physical, chemical and biologic agents including the embryonic stem cell technology for specific gene targeted defects. Despite some serious objectives in regard to clinical aspects of human intestinal bowel disease, animal models of intestinal inflammation have advantages and being complementary to clinical approach indicate the clear need for experimental studies to be continued.

Effect of methylprednisolone on small bowel, spleen and liver changes in a murine model of inflammatory bowel disease.

The aim of this study was to evaluate the influence of methylprednisolone (1 mg/kg, i.p.) on inflammatory lesions in the small bowel, liver (pericholangitis) and spleen (lymphofollicular proliferation), in a model of inflammatory bowel disease induced by 2.4-dinitrofluorobenzene in previously sensitized BALB-c mice. As a parameter of corticosteroid anti-inflammatory and immunosuppressive action, we simultaneously investigated its effects on mononuclear cell accumulation within the ileal lamina propria and submucosa during the observed time period (1-30 days). We noted a significant decrease in accumulation of mononuclear cells within the lamina propria (P < 0.001). An effect on mononuclear cell infiltration within the ileal submucosa was also noted but was not statistically significant. In addition, pericholangitis in the liver and lymphofollicular proliferation in the spleen were not observed in the experimental group during treatment with methylprednisolone. The results of this study indicate that the previously described model of intestinal inflammation could be used in further research of present and new therapeutic modalities for inflammatory bowel disease.

A model of inflammatory bowel disease induced by 2,4-dinitrofluorobenzene in previously sensitized BALB-c mice.

The aim of this study was to develop a model of inflammatory bowel disease (IBD) induced by colonic application of 2,4-dinitrofluorobenzene in previously sensitized BALB-c mice. During the follow-up period of 30 days we observed ulcerations, haemorrhage, necrosis, and mononuclear infiltration in the colonic mucosa of previously sensitized (experimental) and, to a lesser extent, nonsensitized (control) animals. In addition, the animals in the experimental group developed adhesions, thickening of colonic segments, stenosis, and dilatation of the colon, and some animals also developed megacolon. Oedema, mononuclear infiltration, and superficial ulcerations were observed in the ileum of experimental animals and, to a lesser extent, in the control group. In addition, the animals in the experimental group developed extraintestinal changes in the liver and spleen (that is, pericholangitis and lymphofollicular proliferation). We suggest that this model of IBD may have some value for the study of early pathogenetic mechanisms of IBD and for developing new therapeutic modalities for this condition.