Rheumatology (Bulgaria)

Investigation of the Relationship between PTPN22 Polymorphisms and Lung Sarcoidosis: A cross sectional study

Serdar Kaymaz — 2023-08-31

Objective: Sarcoidosis is a systemic granulomatous disease with an unknown etiology characterized by noncaseating granuloma formation. It most often affects the lungs. Protein tyrosine phosphatase non-receptor 22 (PTPN22) is a gene that acts as a negative regulator of T-cell activation. Polymorphisms of this gene are associated with multiple human autoimmune diseases. The aim of this study was to assess the relationship between PTPN22 polymorphisms and lung sarcoidosis in a selected population.

Methods: The study included 64 patients with lung sarcoidosis and 30 healthy controls. Patients were genotyped to determine two single nucleotide polymorphisms (SNPs) using the polymerase chain reaction (PCR) method. Hardy–Weinberg equilibrium (HWE), an important tool for detecting genotyping errors, was tested. Direct counting was used to estimate genotype frequencies. Logistic regression analysis was performed to compare allele and genotype frequencies between the patient and control groups.

Results: The results of the study showed no correlation between lung sarcoidosis and the tested two SNPs of the PTPN22 gene (rs2488457, rs1310182) (p>0.05). The categorization analysis according to the clinical features, laboratory, and radiographic characteristics showed no correlation between the tested polymorphism of PTPN22 and these characteristics (p>0.05).

Conclusion: The present study demonstrated that the studied two SNPs of the PTPN22 gene (rs2488457, rs1310182) were not correlated with lung sarcoidosis, suggesting that it might be different from other classic autoimmune disorders. There is a need for more studies to verify these results concerning lung sarcoidosis in other ethnic origins.

Impact of steroid and lidocaine injection in the sacroiliac joint in axial spondyloarthritis patients: a randomized controlled trial

Ahmed Elsaman — 2023-08-31

Background: The value of steroid and lidocaine injection of the sacroiliac joint in axial spondyloarthritis patients on magnetic resonance imaging scores and clinical disease outcome measures is not yet well assessed.

Patient and methods: Participants were randomly assigned into two groups; Group I received unilateral ultrasound-guided sacroiliac joint injection with .5% lidocaine hydrochloride mixed with triamcinolone. At the same time, group II received subcutaneous saline injection. All participants fulfilled the ASAS criteria for axial SpA and all had bone marrow edema of at least one sacroiliac joint at baseline. Outcomes measures were: Visual Analogue Scale (VAS), Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Functional Index (BASFI), and Spondyloarthritis Research Consortium of Canada (SPARCC) scores. Participants were assessed at baseline (before and after sacroiliac joint injection) and after three months. This clinical trial was registered on clinicaltrials.gov under the number NCT04895228.

Results: In this study, a total of 61 participants were registered. There was a significant difference between both groups regarding pain, spine mobility, SPARCC, and ASDAS scores in favor of group I. Spine mobility showed the earliest improvement, followed by pain whilst SPARCC, and ASDAS scores showed improvement after three months. Higher disease activity, younger age, and shorter disease duration were all associated with better outcomes. Bilateral hip involvement was a predictor of poor response.

Conclusion: Sacroiliac joint injection of lidocaine and triamcinolone in axial SpA patients is a cost-effective and practical technique for controlling pain, improving function, disease activity scores, and bone marrow edema with acceptable complications and relatively sustained effect.

Necrotizing Raynaud's phenomenon after recurrent COVID-19 infection

Vladimira Boyadzhieva — 2023-08-31

Raynaud's phenomenon (RP), which can be primary or secondary, is a common vascular clinical syndrome due to abnormal arteriolar vasospasm. Its treatment is most often conservative depending on the etiology. In recent years, there have been reports of RP as a syndrome after a previous SARS-CoV-2 infection, in patients of different genders and ages. As an etiological factor for the development of vascular pathology in these cases, two main mechanisms are assumed: an autoimmune process or the thrombosis of arterial vessels, leading to tissue ischemia, and the so-called necrotizing Raynaud's phenomenon. In the pathogenesis of Raynaud's phenomenon, the influence of local, neuronal and hormonal mediators is emphasized. Some studies prove the role of estrogens, which explains the higher incidence of RP among women. At present, there is no convincing evidence for "candidate genes" to be associated with Raynaud's phenomenon, despite studies by some authors (Susol et al., 2000; Pistorius et al., 2006). Vasospasm in digital ischemia may be further complicated by COVID-19 infection. Another potential component is hypercoagulation (further complicated by the presence of antiphospholipid antibodies in certain patients) and elevated levels of D-dimer. A state of hypercoagulation is caused by the so-called cytokine storm. This inflammatory state, as a result of endovascular damage, increased platelet activity and coagulation cascade, causes the so-called phenomenon of immunothrombosis. Overactivation of the coagulation pathway during cytokine storm results from increased activity of thrombin, which has an additional role in the inflammatory process through proteinase-activated receptors (PARs). Acrocyanosis due to excessive coagulation status has been described in critically ill patients with COVID-19. In these patients, gangrene may arise from impaired blood flow and insufficient healing of digital wounds, which is associated with elevated levels of C-reactive protein (CRP). Ischemic limb lesions, usually seen in older patients with severe clinical course of the disease, represent a dangerous, although rare, complication associated with COVID-19 and are due to arterial occlusions. They are extremely difficult to treat and often lead to amputations. In patients with antiphospholipid syndrome, arterial and venous thrombi are primarily caused by the formation of neutrophil extracellular traps (NET), which in turn activate platelets, and their excessive formation can lead to local thrombosis. In addition to platelet activation, neutrophils release tissue factor, which initiates the coagulation cascade. NETs bind coagulation factor XII and activate it, and also induce an inflammatory reaction in the vessel wall. According to the available knowledge to date, the hypothesis that digital necrosis in patients with COVID-19 is primarily related to the formation of NETs has been developed.

Necrotizing Raynaud's phenomenon (NRP) is a vascular clinical syndrome characterized by vasoconstriction of distal resistance vessels following low temperatures or states of anxiety and stress. The first symptom is pain, due to lack of oxygen, which leads to tissue ischemia. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause endotheliopathy with microvascular and macrovascular thrombotic events. COVID-19 induces hypercoagulation, thrombosis, endothelial damage, and inflammation leading to vasculitis. The coagulopathy, inflammation, and thrombosis seen in COVID-19 are potentiated by increased activity of clotting factors, loss of protective glycocalyx function, and decreased nitric oxide levels. The effects of COVID-19 in patients with RP are still being elucidated.

This review presents a series of selected clinical cases associated with Raynaud's phenomenon (necrotic, new-onset, exacerbated, or as part of another systemic connective tissue disease) secondary to past COVID-19 infection or vaccination.

Capillaroscopy in COVID-19

Jaklin Svetoslavova Doncheva - Dilova — 2023-08-31

The infectious disease COVID-19, caused by the SARS-CoV-2 virus, is characterized by a wide range of clinical manifestations (pulmonary and extrapulmonary) and in some cases with post-infectious manifestations in persons who survived the infection. The vascular tropism of SARS-CoV-2 is the basis for the interest in using nailfold capillaroscopy to assess the microcirculation in children and adults who have recovered from COVID-19. Most often, non-specific changes are observed, without certain manifestations of microangiopathy and without a specific combination of microvascular findings, on the basis of which to define a specific capillaroscopic picture of the "COVID - 19" type. The possibility that capillaroscopy in combination with other findings can be used for personalized approach and determination of prognosis in patients with post-COVID syndrome needs further studies.

A case of SAPHO syndrome treated with zoledronic acid and hydroxychloroquine

Sevdalina Lambova — 2023-09-06

Abstract: SAPHO syndrome is characterized with a set of symptoms including skin lesions, osteoarticular manifestations like aseptic osteitis (of the anterior chest wall or other skeletal sites), peripheral synovitis. Due to the lack of randomized clinical trials and low prevalence of the condition, there are no established treatment guidelines for SAPHO syndrome. Here, we report a clinical case of SAPHO syndrome with osteitis of the sternum and palmoplantar pustulosis successfully treated with zoledronic acid and hydroxychloroquine.

Taxane-induced scleroderma-like skin changes – review of the literature and case report

Sevdalina Lambova — 2023-09-06

Abstract: Taxanes (paclitaxel, docetaxel) are antineoplastic agents used in advanced ovarian, breast, lung, head and neck cancer. Diverse cutaneous adverse reactions associated with taxane administration have been reported such as bullous eruption, onycholysis, acral erythema, erythema multiforme, pustular eruption, scleroderma-like skin changes of both upper and lower extremities. Here, we report a case of 48-year-old female patient, who presented for consultation with rheumatologist with complaints of hand and finger oedema and stiffness. Oedema and mild skin thickening of the fingers and hands were evident at physical examination. Inflammatory joint pain, synovitis, Raynaud’s phenomenon and trophic changes were not present. Standard laboratory tests i.e., complete blood count and biochemistry tests were within normal values. The patient was euthyroid. Immunological tests were negative (antinuclear antibodies; antibodies against extractable nuclear antigens – dsDNA, Sm, RNP, Scl-70; antiphospholipid antibodies – anticardiolipin, anti-beta-2-glycoprotein; anti-CCP antibody and rheumatoid factor). Capillaroscopic examination did not reveal signs of microangiopathy. Skin biopsy was perfomed in the area of a proximal phalanx and the histological examination revealed dermal oedema and superficial scant perivascular infiltrate containing lymphocytes and histiocytes. The patient had undergone an operation for breast cancer 13 years ago and subsequent second operation because of cancer recurrence 7 years ago. After the second operation chemotherapy was performed that included 1 cycle with paclitaxel and 4 cycles with docetaxel. The analysis of the case led to the conclusion that the scleroderma-like skin changes of the fingers and hands are induced by taxane administration in the past. The patient received corticosteroid treatment for 7 months with gradual resolution of symptoms.

Overlapping features of thrombotic thrombocytopenic purpura and systemic lupus erythematosus, a diagnostic and a management challenge

M. Krstevski — 2023-08-31

Thrombotic thrombocytopenic purpura (TTP) is a rare, potentially fatal blood disorder that can be challenging for clinicians to identify in the setting of autoimmune diseases such as systemic lupus erythematosus (SLE). SLE can present with thrombotic microangiopathy (TMA) and differentiation between the two diseases can be quite difficult.

In this case report we present a 62-year-old female with a history of SLE who was hospitalized with thrombocytopenia, dysarthria, dizziness, paresthesia and altered mental status. The laboratory results revealed direct Coombs negative hemolytic anemia, severe thrombocytopenia, significant elevation of lactate dehydrogenase, leukocytosis and presence of few schistocytes in the peripheral film. In addition, we also present evidence for circulating anti-ADAMTS13 antibody/ADAMTS13 antigen. Based on clinical, hematological, and biochemical findings, we concluded that it was a case of TTP-like microangiopathy associated with SLE and indicated treatment with methylprednisolone pulses and plasmapheresis. Later on, she developed psychosis and made plasmapheresis difficult to perform. We continued corticosteroids (dose 1mg/kg), RhoGAM, Chloroquine and Azathioprine, obtaining a satisfactory response after one week of treatment.

Efficacy of rituximab in difficult to treatment patients with polymyositis

Ирина Иванова Момчева — 2023-09-01

Inflammatory myopathies are a heterogeneous group of diseases rarely encountered in clinical practice. They primarily involve the transverse striated muscles, and in some cases there is also extramuscular involvement of the skin, lungs, joints, esophagus, heart. Acute forms of myositis, which are the most common, are associated with viral diseases and usually resolve spontaneously. Chronic forms usually have a subacute onset and unknown etiology. The presence of different clinical phenotypes and courses is associated with diversity in autoantibody production. Historically, the treatment of refractory forms of polymyositis and dermatomyositis has undergone significant dynamics. Data from various studies have been published that show a significant reduction in the symptoms of inflammation, but unfortunately some of these disease-modifying treatments could not be established in rheumatology practice as sufficiently effective. Limiting factors are the retrospective nature of these studies, as well as different inclusion and exclusion criteria. However, in recent years, more and more data have emerged that present rituximab as one of the promising molecules for the treatment of patients refractory to conventional synthetic disease-modifying antirheumatic agents We present a clinical case of a 40-year-old Caucasian man with onset of the disease – fever, asthenodynamia, muscle pain and weakness, pericardial and pleural effusions. The patient was treated with glucocorticoids, methotrexate, pulse therapies with methylprednisolone and cyclophosphamide, as well as pulse therapy with intravenous immunoglobulins. Due to the temporary effect of the treatment and the relapse of the disease, the patient was started on mycophenolate mofetil therapy (instead of methotrexate). However, a new peak in disease activity was reported, necessitating resumption of pulse therapies with methylprednisolone and cyclophosphamide. Due to the refractory course of the disease, the patient was treated with rituximab after signed informed consent. A significant reduction in disease activity and a good clinical and therapeutic effect were reported.