Bronchiectasis, lymphadenopathies related to BAFF overexpression and lymphoplasmacytic cystitis as adverse events associated with prolonged use of rituximab in systemic autoimmune rheumatic diseases.

BACKGROUND: The long-term use of rituximab (RTX) has been gaining ground in the treatment of systemic autoimmune diseases. The adverse events (AEs) associated with its use different to infections are being reported. METHODS: A cohort of patients with SAIDs treated at a high-complexity center in Cali (southwestern Colombia) with follow-up from January 2008 to December 2022 were examined to search for potential AEs associated with prolonged use of RTX. RESULTS: From 178 patients with long-term use of RTX 3 (1.68%) had lymphadenopathies with lymphoid follicular hyperplasia related to BAFF overexpression, 4 (2.24%) with bronchiectasis, and 4 (2.24%) with lymphoplasmacytic cystitis. CONCLUSION: Bronchiectasis, lymphoid follicular hyperplasia related to BAFF overexpression, and lymphoplasmacytic cystitis may be life-threatening long-term AEs in patients with prolonged use of RTX.

Neutrophil CD64 expression, procalcitonin and presepsin are useful to differentiate infections from flares in SLE patients with SIRS.

Background/Objective Differentiating systemic lupus erythematosus (SLE) activity from infections in febrile patients is difficult because of similar initial clinical presentation. The aim of this study is to evaluate the usefulness of a number of biomarkers for differentiating infections from activity in SLE patients admitted with systemic inflammatory response (SIRS). Methods Patients with SLE and SIRS admitted to the emergency room were included in this study. Measurements of different markers including procalcitonin, neutrophil CD64 expression and presepsin, were performed. Infection was considered present when positive cultures and/or polymerase chain reaction were obtained. Sensitivity and specificity were calculated for all biomarkers. Results Twenty-seven patients were admitted, 23 women (82.5%), mean age 33.2 years. An infectious disease was confirmed in 12 cases. Markers for SLE activity including anti-DNA titers by IIF ( p = 0.041) and enzyme-linked immunosorbent assay ( p = 0.009) were used for differentiating SLE flares from infection. On the contrary, increased procalcitonin ( p = 0.047), neutrophil CD64 expression by flow cytometry ( p = 0.037) and presepsin ( p = 0.037) levels were observed in infected SLE patients. Conclusions High neutrophil CD64 expression, presepsin and procalcitonin levels are useful to differentiate infections from activity in SLE patients. In most cases, a positive bioscore that includes these three markers demonstrate the presence of an infectious disease.

Profile of BAFF and its receptors' expression in lupus nephritis is associated with pathological classes.

Background/Objective B-cell activating factor (BAFF) plays an important role in the pathogenesis of systemic lupus erythematosus. However, the role of BAFF in lupus nephritis (LN) is not understood. Our aim was to evaluate the expression of BAFF and its three receptors in renal biopsy samples from patients with LN and investigate a relationship with pathological class. Methods We conducted a prospective descriptive study (2011-2014) on 52 kidney biopsy samples from patients with LN. Immunohistochemistry for BAFF, its receptors (transmembrane activator and calcium modulator and cyclophilin ligand interaction (TACI), protein maturation of B cells (BCMA), and BAFF-receptor (BAFF-R)), and CD20 expression was performed. Samples were scored according to the percentage of cells with positive expression. Results In class II LN, BAFF-R and TACI were not expressed, whereas BCMA and BAFF were lowly expressed in the interstitial inflammatory infiltrates. Proliferative class III/IV had elevated BAFF expression in the glomeruli, and TACI was expressed in interstitial inflammatory infiltrates and the glomeruli. Interestingly, the class IV cases with vasculopathy ( n = 4) had endothelial BAFF expression, which was not visible in thrombotic microangiopathy ( n = 4). Class V was characterized by low BAFF expression in interstitial inflammatory infiltrates and by BAFF, TACI, and BCMA expression in the glomeruli. BAFF expression was associated with inflammatory scores and CD20 positive infiltrates, mainly in class IV. Conclusions Expression patterns of BAFF and its receptors differ according to LN class. Our study provides evidence that BAFF could be used as a routine marker in LN biopsies and to determine which patients will benefit from anti-BAFF therapy.

Worsening of calcinosis cutis with teriparatide treatment in two osteoporotic patients.

We present two cases of patients with systemic autoimmune diseases (one with dermatomyositis and one with CREST syndrome) who presented with a worsening of calcinosis cutis after treatment of osteoporosis with teriparatide. To our knowledge, this association is not described in the literature and might be considered in the spectrum of adverse reactions to teriparatide.

Direct oral anticoagulants in antiphospholipid syndrome: a real life case series.

AIM: The aim of this study was to describe a case series of patients with primary or secondary antiphospholipid syndrome (APS) treated with direct oral anticoagulants (DOACs). PATIENTS AND METHODS: Clinical charts of eight patients with thrombotic primary or secondary APS treated with direct oral anticoagulants (DOACs) between January 2012 and May 2015 were reviewed. RESULTS: The mean age was 45 ± 14.36 (range 27-69 years). Four patients had secondary APS (50%). All patients were initially treated with warfarin by a mean time of 70.87 ± 57.32 months (range 17-153 months). Changes in anticoagulation were defined by recurring thrombosis in five patients (62.5%) and life-threatening bleeding in the other three cases. Seven patients (87.5%) received rivaroxaban treatment and one patient (12.5%) apixaban. The mean follow-up period with DOACs was 19 ± 10.06 months (range 2-36 months). There was no recurrence of thrombosis by the time of data collection. CONCLUSIONS: Despite not being the standard treatment in APS, we propose DOACs as a rational alternative for the management of patients with this diagnosis. Further interventional clinical studies are necessary for possible standardization of this therapy in APS patients.

Soluble or soluble/membrane TNF-α inhibitors protect the brain from focal ischemic injury in rats.

Tumor Necrosis Factor-alpha (TNF-α) is an immunomodulatory and proinflammatory cytokine implicated in neuro-inflammation and neuronal damage in response to cerebral ischemia. The present study tested the hypothesis that anti-TNF-α agents may be protective against cerebral infarction. Transient focal ischemia was artificially induced in anesthetized adult male Wistar rats (300-350 g) by middle cerebral artery occlusion (MCAO) with an intraluminal suture. TNF-α function was interfered with either a chimeric monoclonal antibody against TNF-α (infliximab-7 mg/kg) aiming to TNF-α soluble and membrane-attached form; or a chimeric fusion protein of TNF-α receptor-2 with a fragment crystallizable (Fc) region of IgG1 (etanercept-5 mg/kg) aiming for the TNF-α soluble form. Both agents were administered intraperitoneally 0 or 6 h after inducing ischemia. Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride staining. Cerebral infarct volume was significantly reduced in either etanercept or infliximab-treated group compared with non-treated MCAO rats 24 h after reperfusion. These results suggest that anti-TNF-α agents may reduce focal ischemic injury in rats.

The importance of evolution in the development and course of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a complex autoimmune disease of recent evolutionary origin. Genetic drift determines diverse polymorphisms implicated in the susceptibility to RA including the major histocompatibility complex (MHC) class II genes in the so-called shared epitope. These genes originated after the divergence between Homo and Pan from their common ancestry Ardipithecus ramidus about 5 million years ago. Natural selection determined the particular changes in the legs (bipedal position), hands, neck, brain and eusociality in humans which influence the clinical presentation of RA. In this article, we hypothesized that the origin and course of RA may be explainable in the light of evolution.

Pneumocystis jirovecii pneumonia in two patients with systemic lupus erythematosus after rituximab therapy.

New cases of Pneumocystis jirovecii pneumonia (PJP) have recently been reported in patients with systemic lupus erythematosus (SLE) after rituximab therapy. Several factors may contribute to susceptibility to P. jirovecii infection in this type of patients, including the immunological characteristics of the disease, the mechanisms of rituximab action, environmental factors, and the biological characteristics of the fungus. We report two patients with SLE who developed PJP after rituximab therapy.

Multiple endovascular stent-graft implantations in a patient with aortic thoracic and abdominal aneurysms due Takayasu arteritis.

We report an adult female patient with Takayasu arteritis (TA) receiving conventional medical treatment and anti-TNF therapy, which developed progressive thoracic and abdominal aortic aneurysms. She developed imminent rupture of the thoracic aneurysm and an endovascular stent-graft (EVSG) was emergency implanted and a year after this procedure the abdominal aneurysm increased in size requiring reoperation and placement of another EVSG. Both procedures had a very good outcome. This case shows the effectivity and security of multiple EVSG implantations in multiple aortic aneurisms in patients with TA.

Is primary hyperparathyroidism a pathogenic factor in some conditions mediated by B lymphocytes hyperactivity?

Several clinical cases have shown the association of primary hyperparathyroidism and immune conditions related to B-cell hyperactivity. In some of these cases the treatment of hyperparathyroidism led to the resolution of the autoimmune phenomena. Thus, this paper hypothesizes that high levels of parathyroid hormone (PTH) may modify B lymphocytes function and induce the development of autoimmunity mediated by B-cell hyperactivity.

Overinfection by Paracoccidioides brasiliensis in Gouty Crystal Arthritis.

Paracoccidioidomycosis is an endemic South American systemic mycosis caused by the dimorphic fungus Paracoccidioides brasiliensis (P. brasiliensis). The main clinical form of disease is pulmonary, but all organs may be involved. We report a case of overinfection by P. brasiliensis in chronic gouty arthritis affecting the proximal phalanx of the right hallux. The patient required proximal amputation and long-term antifungal therapy.

Psychiatric manifestations in patients with dysautonomy associated with systemic lupus erythematosus.

The psychiatric manifestations of three patients with systemic lupus erythematosus (SLE) and neuropathic dysautonomic processes are described. All patients had a severe form of SLE with neurological, renal, articular, pulmonary or haematological manifestations. All three have two types of psychiatric manifestations: (1) a chronic and progressive depression and (2) a complex dissociative disorder during the acute episodes of postural hypotension. A provocative test with SPECT with 99mTc-HmPAO to be done during the episode of orthostatic hypotension may contribute to clinical assessment of complex changes in cerebral regional perfusion.

Acute Generalized Exanthematous Pustulosis due to Tocilizumab in a Rheumatoid Arthritis Patient.

We report a female patient with rheumatoid arthritis which was refractory to methotrexate, leflunomide, and anti-TNF therapy. She was treated with anti-IL-6 tocilizumab (TCZ), with an early appearance of sterile pustules on erythematous swollen skin of trunk, back, and abdominal area. The lesions were consistent with the diagnosis of acute drug-related generalized exanthematous pustulosis (AGEP). This adverse event was controlled with medical treatment without requiring removal of TCZ.

Patients with relapsing polychondritis and previous cartilage trauma present more autoimmunity phenomena.

Relapsing polychondritis (RP) is an autoimmune disease characterized by inflammation and destruction of all type of body cartilage, and the cartilage trauma may be a trigger of the disease in a susceptible person. We describe the clinical and laboratory findings in a group of 18 patients with RP with (7 cases) or without (11 cases) anteceding cartilage trauma. The mean age was 41 years in the group with cartilage trauma and 55 years in the group without cartilage trauma. For both groups, female gender was predominant. All patients presented with auricular chondritis. Systemic manifestations and autoimmunity were more common in patients with anteceding trauma.

Biochemical comparison of venoms from young Colombian Crotalus durissus cumanensis and their parents

Crotalus durissus cumanensis, a rattlesnake endemic to Colombia and Venezuela, is considered one of the most lethal snake species in Latin America. The aim of the present study was to compare the protein content and biological activity of the venom obtained from eight specimens of C. durissus cumanensis, namely two adults from different localities of Colombia and six offspring born in captivity. Protein profiles of crude venoms were analyzed by SDS-PAGE and RP-HPLC, and biological activities were evaluated for lethality, edema, defibrination, hemolytic and coagulant activities to assess individual venoms of adults and a pool of young snake venoms. Transient edema appeared rapidly after venom inoculation, whereas hemorrhagic effect was not observed. Differences in protein profiles, lethality, hemolytic, coagulant and defibrinating activities between both adult snake venoms were observed; those from the mother snake exhibited higher activities. Venoms from young snakes were similar to the one obtained from the mother, but the coagulant effect was stronger in offspring venoms. Notably, biological effects of the father snake venom were not comparable to those previously described for C. durissus cumanensis from Venezuela and C. durissus terrificus from Brazil, confirming the high variability of the venom from Crotalus species.

Takayasu arteritis in Colombia.

Takayasu arteritis has been recognized in Colombia just recently, and so far we do not have any report concerning its presentation here. In this first report, some issues related to the presentation of the disease are indicated and compared with those found in the medical literature. No differences were found in age and sex. Most of the cases were diagnosed during an inactive phase of the disease with advanced manifestations due to vascular lesion which suggests the existence of some genetic factor influencing such a presentation, or may be the consequence of a delay in diagnosing the disease during initial and active stages due to not suspecting it. Comparing the vessels which are affected among other races and countries, we can find both differences and similarities. With the purpose of discovering the demographic, clinical, angiographic and laboratorial characteristics of Takayasu arteritis in Colombia, the present study was carried out by studying 35 clinical cases in different medical centers of the country.

Chronic septal panniculitis caused by phaeohyphomycosis.

Panniculitis is caused by a heterogeneous group of clinical entities that tend to manifest themselves as erythematous-violaceous subcutaneous nodules on the legs. In addition to associations with rheumatic diseases including vasculitis, its causes may include various infections. The microorganisms most commonly involved are bacteria and fungi. Among the latter, Candida Sp,, Nocardia Sp., Sporotrichosis, cryptococcosis, histoplasmosis, cromomycosis, and inter alia, have been described. We present an immu-nocompetent patient with a persistent, neutrophilic, chronic septal panniculitis caused by Aureobasidium Pullulans, an infection-generating fungus belonging to the phaeohyphornycosis group. The patient was treated with amphotericin B 0.5 mg/kg/day, itraconazole 400 mg/day p.o., and 5 fluo-rocytosine 150 mg/kg/day for 4 weeks with excellent response.This is the first report in the literature on panniculitis caused by A. Pullulans's phaeohyphomycosis. We suggest that, whenever we observe patients with symptomatic panniculitis, especially if they are resistant to regular treatment, are of chronic course, and have neutrophilic infiltrates in their biopsies, panniculitis caused by uncommon organisms such as phaeohyphomycosis should be considered in the differential diagnosis.