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Hypereosinophilic syndrome (HES) is a rare haematologic disorder characterised by unexplained, persistent eosinophilia with organ involvement. We report the case of a 74-year-old patient who presented with a pemphigoid-like bullous rash as the only manifestation of an HES. This report highlights the importance of the dermatological manifestations of this potentially life-threating condition that may initially present as a skin-limited disease. Bullous pemphigoid (BP) is a very common autoimmune blistering dermatosis that may share common clinical and histological features or associate with an HES. HES should be considered when patients diagnosed with BP demonstrate atypical course under corticosteroids and/or recalcitrant blood eosinophilia.

Background: The first case of COVID 19 illness was detected on 31st December 2019 and the disease has progressed globally causing significant morbidity and mortality. The disease initially thought to be a respiratory virus soon showed manifestations involving other systems and diagnosis and treatment of the disease became more complicated. This study aims to derive a scoring system based on health records of patients suffering from COVID 19, to help in early triaging of the illness and therefore allowing for early institution of treatment. Aims and Objective: To establish a scoring system inclusive of clinical, laboratory and radiological parameters to assist in the prognosis of patients afflicted with COVID 19 illness. Materials and Methods: Health records of 138 COVID patients has been included in the study. The scoring system comprises of parameters including Age, Co-morbidities, Shortness of breath, Saturation, Pulse Rate, Respiratory rate, temperature, D dimer, Neutrophil Lymphocyte ratio, Troponin I, Organ involvement, Radiology. The cumulative scoring ranges from 0-16. The mortality rate among the subjects included was 25.4%. Results: All parameters involved were found to be independent risk factors for mortality. Patients were effectively categorized based on the scoring system and mortality found to be associated with increasing scores. This model displayed good discrimination (AUC =0.875) and the sensitivity and specificity of the model was found to be 0.857 and 0.767 respectively. Conclusion: This scoring system has been designed to categorize based on the systemic involvement of the disease and thus would serve as a reliable indicator for prognostic assessment in patients. [ABSTRACT FROM AUTHOR] Copyright of Asian Journal of Medical Sciences is the property of Manipal Colleges of Medical Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Sarcoidosis is a systemic granulomatous disease with heterogenous clinical manifestations. Here we review the diagnosis of sarcoidosis and propose a clinically feasible diagnostic work-up and monitoring protocol. As sarcoidosis is a systemic disease, a multidisciplinary approach is recommended for best outcomes. However, since the lungs are frequently involved, the pulmonologist is often the referral physician for diagnosis and management. When sarcoidosis is suspected, diagnosis needs to be confirmed and organ involvement/impairment assessed. This process is also required to establish whether the patient is likely to benefit from treatment, as many cases of sarcoidosis are self-limited and remit spontaneously. Whether or not treatment is started, effective regular follow-up is necessary to monitor changes in the disease, including extension, progression, remissions, flare-ups, and complications.

Sarcoidosis is a disease that can affect a multitude of organs and manifest as cutaneous disease. Cutaneous manifestations of sarcoidosis vary widely in morphology, earning the nickname of "great imitator," and the diagnosis often requires clinicopathologic correlation and additional laboratory and radiographic workup. We present the case of a 42-year-old African American woman with ichthyosiform sarcoidosis on the bilateral lower extremities. As one of the rarest specific variants of cutaneous sarcoidosis, ichthyosiform is understudied and has been primarily documented in case reports and series. We undertake a comprehensive review of the literature to identify key clinicopathologic features including the characterization of sites of cutaneous and systemic involvement, as well as typical histopathological findings. Lower extremities were the most involved body site (85.7%). Extracutaneous organ involvement centered around pulmonary (65.7%), lymph node (57.1%), and ocular (31.4%) involvement. Of the histopathological features reported, hyperkeratosis (51.4%) and diminished stratum granulosum (62.9%) were most frequently reported in conjunction with dermal granulomas (100%). We hope that these findings will serve to aid clinicopathological correlation and accurate diagnosis of ichthyosiform sarcoidosis.

Introduction:Cardiac involvement is rare in hydatid cyst disease, which accounted for 0.5%-2% of all hydatidosis cases. Cardiac cysts usually occur as part of a wider infestation with extracardiac involvement. This study aimed to describe the general characteristics, imaging findings, and range of organ involvement in cases of cardiac hydatid disease.Methods:Retrospective assessment of cardiac hydatid disease records, between 2007 and 2019, was undertaken to identify patients with cardiac hydatidosis. Hydatid cysts were assessed by transthoracic echocardiography, magnetic resonance imaging, and computed tomography. Clinical symptoms, treatment modalities, and follow-up were also evaluated.Results:Over the study period, 22 (13 males: 59.1%; mean age: 43.1 years; range: 12-63 years) patients with 24 cardiac hydatid cysts were identified. The most common symptom was chest pain, which occurred in 13 (59.1%) patients. Cardiac cysts were located in the left ventricle (n=10, 41.7%), right ventricle (n=5, 20.8%), interventricular septum (n=5, 20.8%), and pericardium (n=4, 16.7%). Extracardiac involvement was present in 14 (63.6%) patients, most commonly affecting the liver (n=10, 45.4%), but in 8 (36.3%) patients, there was no extracardiac organ involvement. Cardiac hydatid cysts were surgically removed in 20 (90.9%) patients.Conclusion:Cardiac hydatid disease is very uncommon, with the left ventricle as the most commonly affected structure in this series. Chest pain was the most common presenting symptom. Extracardiac involvement is common, so patients with cardiac hydatid cysts should be investigated for involvement of other organs.

A 40-year-old Japanese woman developed malignant-phase hypertension complicated by thrombotic microangiopathy, progressing to end-stage renal disease. Five years later, she was diagnosed with pulmonary arterial hypertension and interstitial pneumonia. Despite a lack of overt skin sclerosis, nucleolar staining in our indirect immunofluorescence analysis and nailfold capillaroscopy facilitated the diagnosis of anti-PM/Scl antibody-positive systemic sclerosis. We observed the persistent presence of anti-PM/Scl antibodies throughout the clinical course, suggesting that her kidney disease was scleroderma renal crisis. Anti-PM/Scl antibodies can be associated with multiple organ diseases. Careful attention to a patient's antinuclear antibody pattern and dermatological findings may help clarify the etiology of undiagnosed diseases.

If blistering occurs in childhood, the possibility of hereditary epidermolysis bullosa should be considered even if the symptoms are mild. Besides clinical and histological examination, molecular genetic screening is diagnostically relevant. For localized forms, symptomatic, topical therapy options are currently still the primary choice. Of particular interest is the new option of topical therapy with diacerein 1 % cream. In the case of a pronounced clinical picture with extracutaneous organ involvement, multidisciplinary management is required. In the future, new forms of therapy such as autologous epidermal stem cell transplantation and gene therapeutic procedures may be applied. Human genetic counselling is indispensable.

Hypocomplementemic urticarial vasculitis syndrome (HVUS) belongs to the group of systemic small-vessel vasculitis and is characterized by persistent urticarial lesions lasting more than 24 hours, hypocomplementemia and frequent coexistence of organ involvement. Lungs, kidneys, joints, gastrointestinal tract, eyes and central nervous system may be involved in the course of the condition. The diagnosis of HUVS is based on the diagnostic criteria – fulfilment of both major criteria (the presence of chronic urticarial lesions with hypocomplementemia) and at least two minor criteria. HUVS may be associated with other systemic conditions. The diagnosis of the syndrome may also precede the development of systemic lupus erythematosus (SLE) in both the paediatric and adult populations. Due to the rarity of the disease, no randomized clinical trials are assessing the effectiveness of individual therapeutic options, and recommendations for the management of HUVS are based on case reports. Glucocorticosteroids (GCSs) are most commonly used as monotherapy or in combination with cyclosporine A, methotrexate, azathioprine, cyclophosphamide or mycophenolate mofetil. In the paper, the clinical picture, recommended diagnostics and therapeutic options for HUVS are discussed.

Behcet's disease is an inflammatory vasculitic disease of unknown etiology characterized by recurrent oral and genital ulcers, ocular findings, and multiple organ involvement. Mucocutaneous findings are the most common symptoms. The most used diagnostic criteria are International Criteria for BD (ICBD), International Study Group (ISG) criteria and pediatric Behcet’s disease criteria (PEDBD). Although diagnostic criteria have been defined, the diagnosis is still difficult due to clinical findings developed in pediatric patients. The aim of this study was to evaluate the clinical findings, phenotype characteristics, sensitivity and specificity of diagnostic criteria, and the course of pediatric Behcet's disease (BD). We evaluated retrospectively the files of 67 (29 M/38 F) patients diagnosed with BD according to expert opinion. The patients were reclassified according to ISG, ICBD, and PEDBD criteria. The control group consisted of a total of 69 patients with BD-mimicking diseases or presenting at least one major BD sign followed at the same center. Sensitivity and specificity were evaluated for the criteria. The mean age of diagnosis was 13.38 ± 3.2 years. There were oral aphthous ulcers in 98.5%, genital ulcers in 68.7%, skin lesions in 31.3%, vascular involvement in 17.9%, neurological involvement in 11.9%, positive pathergy test in 33.8%, and positive HLA-B51 in 57.1% of patients. The sensitivity of ICBD, ISG and PEDBD criteria was 88.1, 43.3, and 37.3%, respectively. The specificity of ICBD, ISG, and PEDBD criteria was 100%. Diagnosis of BD in childhood is still difficult. ICBD criteria have the highest sensitivity among the diagnostic criteria. These criteria can also be used in childhood.

Introduction: In recent years, the systemic treatment of patients with metastatic renal-cell carcinoma (mRCC) has undergone profound innovations, offering the availability of new drugs, and raising the bar of the survival expectation in this, previously, almost-always, incurable disease. The likeliness of reaching durable response and long-term survival is still closely linked to good clinical management and smart treatment sequencing, rather than to a single systemic treatment choice.Areas covered: We review all systemic therapeutic options currently available, describe the evidence behind the current options available for mRCC patient treatment, and provide our personal cues to support clinical decisions.Expert opinion: The IMDC classification is still the only widely validated tool for the choice of primary therapy. Other elements should then be considered for selecting patients who can still receive TKI monotherapy (good-risk patients) or who deserve an 'all-at-once' approach with TKI plus ICI (poor-risk patients with the high metastatic burden and poor-prognosis organ involvement, likely not able to achieve a second chance), identifying these two 'extreme' situations and setting all the other treatment choices on the basis of several nuances. In the second- and further-line settings, ad-hoc prospective trials are awaited.

Systemic sclerosis (SSc) is a highly complex disease whose heterogeneity includes multiple aspects of the condition, such as clinical presentation, progression, extent and type of organ involvement, and clinical outcomes. Thus far, these features remain not easily predictable both at the patient group level and in a given patient with regard to age at onset and clinical course. The unpredictable clinical course represents an obstacle to focusing potentially effective treatment in patients that need it the most. At the time of organ involvement and clinical diagnosis, most of the clinical manifestations are irreversible; therefore, predicting outcomes becomes crucial. This can explain the multiple attempts to identify prognostic, predictive, and monitoring—both soluble and imaging—biomarkers over the past years. They range from the currently most used biomarkers, the autoantibodies associated with disease-specific clinical features and course, to the single recently proposed skin, lung, cardiac involvement biomarkers and to the composite scores capturing multiple aspects of the disease. This review will focus on soluble and imaging biomarkers that recently showed promising evidence for outcome stratification in patients with SSc.

Immunoglobulin G4-related disease (IgG4-RD) is an increasingly recognized syndrome which shares similar pathologic, serologic, and clinical features in the affected organs. Subacute development of a mass or diffuse enlargement of the organ is a common presenting feature. It is more commonly seen in middle-aged or older men. Lymphadenopathy is common in them. Tissue infiltration with lymphoplasmacytic collection, predominantly of IgG4-positive plasma cells, accompanied by “storiform” pattern of fibrosis, obliterative phlebitis, and increased tissue eosinophils are the hallmark histologic findings. Rapid response to systemic steroids is characteristic. If present, the typical cutaneous findings such as papulonodules or plaques in the head-and-neck region may serve as an initial clue to the underlying systemic involvement in IgG4-RD. Hence, dermatologists need to be aware of this entity for early recognition of underlying organ involvement and thus the prompt management.

Because of a similar organ involvement and histopathological features, IgG4-related disease (IgG4-RD) may mimic some forms of granulomatosis with polyangiitis (GPA). However, several cases of clear coexistence or overlap of both diseases have been reported. We describe a case of a 47-year-old man presenting with a renal mass and a nasal crusting showing histopathological features of IgG4-RD in both territories. Cytoplasmic/proteinase 3 (PR3) antineutrophil cytoplasmic antibodies (ANCA) were positive and the patient subsequently developed kidney failure and nephritic syndrome that led to a renal biopsy re-evaluation revealing changes compatible with segmental necrotising glomerulonephritis and GPA. Remission induction therapy with prednisone and rituximab was started and clinical and laboratory parameters returned to normal. After administering a maintenance regimen based in rituximab 500 mg every six month the patient remained asymptomatic during 4 years of follow-up and free of prednisone the last 18 months. Although coexistence or overlap of GPA and IgG4-RD may be established in some clinical scenarios, the possibility of widening the spectrum of a single disease is also postulated.

Background Psoriasis is a common immune-mediated skin condition that affects at least 2% of the Australian population. Though psoriasis was often considered a cutaneous condition alone, more recent literature has shown other organ involvement. These comorbidities may be missed unless specifically looked for. Objective The aim of this article is to outline the well-recognised comorbidities associated with psoriasis to facilitate a discussion for general practitioners (GPs) to have with their patients about lifestyle changes, the need to screen for other diseases and management of comorbidities. Discussion GPs are in a prime position to screen, diagnose and manage comorbidities in a patient with psoriasis. GPs have a broad understanding of and exposure to general medicine and are in a privileged position of seeing many patients with psoriasis within the spectrum of the disease.

Angiotensin-converting enzyme 2 (ACE2) has been established as the functional host receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the current devastating worldwide pandemic of coronavirus disease 2019 (COVID-19). ACE2 is abundantly expressed in a variety of cells residing in many different human organs. In human physiology, ACE2 is a pivotal counter-regulatory enzyme to ACE by the breakdown of angiotensin II, the central player in the renin-angiotensin-aldosterone system (RAAS) and the main substrate of ACE2. Many factors have been associated with both altered ACE2 expression and COVID-19 severity and progression, including age, sex, ethnicity, medication, and several co-morbidities, such as cardiovascular disease and metabolic syndrome. Although ACE2 is widely distributed in various human tissues and many of its determinants have been well recognised, ACE2-expressing organs do not equally participate in COVID-19 pathophysiology, implying that other mechanisms are involved in orchestrating cellular infection resulting in tissue damage. Reports of pathologic findings in tissue specimens of COVID-19 patients are rapidly emerging and confirm the established role of ACE2 expression and activity in disease pathogenesis. Identifying pathologic changes caused by SARS-CoV-2 infection is crucially important as it has major implications for understanding COVID-19 pathophysiology and the development of evidence-based treatment strategies. Currently, many interventional strategies are being explored in ongoing clinical trials, encompassing many drug classes and strategies, including antiviral drugs, biological response modifiers, and RAAS inhibitors. Ultimately, prevention is key to combat COVID-19 and appropriate measures are being taken accordingly, including development of effective vaccines. In this review, we describe the role of ACE2 in COVID-19 pathophysiology, including factors influencing ACE2 expression and activity in relation to COVID-19 severity. In addition, we discuss the relevant pathological changes resulting from SARS-CoV-2 infection. Finally, we highlight a selection of potential treatment modalities for COVID-19. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

ObjectivesSystemic sclerosis is a heterogeneous, multisystem disease. It can occur at any age, but most patients develop the disease between the age of 40 to 50 years. There is controversial evidence on whether/how the age at disease onset affects their clinical phenotype. We here investigate the relationship between age at disease onset and symptoms in a large cohort of SSc patients (lcSSc, dcSSc and SSc-overlap syndromes).MethodsClinical data of the registry of the German Network for Systemic Scleroderma including 3281 patients were evaluated and subdivided into three age groups at disease onset (60 years).ResultsAmong all SSc patients, 24.5% developed their first non-Raynaud phenomenon symptoms at the age 60 years), except for gastrointestinal and musculoskeletal involvement. No significant difference was found for the use of corticosteroids. However, significantly, fewer patients older than 60 years received immunosuppressive treatment.ConclusionIn this large registry, ∼25% of patients developed SSc at an age above 60 years with an increased frequency of lcSSc. In this age group, an onset of internal organ involvement was significantly accelerated across all three subsets. These findings suggest that, in the elderly cohort, more frequent follow-up examinations are required for an earlier detection of organ complications.

Background Capillaroscopy is an essential tool for the diagnosis of systemic sclerosis. Using this exam as a prognostic factor will allow earlier intervention and probably, delay on disease progression. We aimed to evaluate the prognostic value of capillaroscopy for the prediction of systemic compromise and subtype differentiation in systemic sclerosis. Methods A systematic literature search was applied in the following electronic databases: Medline, PubMed, Embase, Cochrane, and Lilacs. The research question was designed based on the PICOT model, and the search strategy was built using the MeSH terms “Microscopic Angioscopy,” “Scleroderma systemic,” “Scleroderma diffuse,” Scleroderma Limited,” “Early Diagnosis” and Boolean operators. The language was restricted to papers published in Spanish or English, from 1990 to 2019. The search terms were explored for each database, and new terms were added, as appropriate. The searches were made again before the final analyses and further studies were retrieved for inclusion at that time. Reference lists of included studies and recent aligned systematic reviews were also screened. Gray literature was not considered in this review. Results A total of 183 articles were found in the selected databases: Medline (n: 115), Embase (n: 66), Cochrane (n: 2), Lilacs (n: 0). After excluding articles due to duplication, a total of 66 studies were selected. Within these articles, a screening process was applied based on the title and abstract, taking into account the eligibility criteria, finally obtaining 21 references. Two researchers assessed the selected articles, and all disagreements were solved by consensus. Finally, a total of 14 articles were included. Conclusions The different abnormalities found in capillaroscopy, especially loss of capillaries, have been consistently associated not only with organ involvement but also with severity of the disease, especially with vascular manifestations (digital ulcers and pulmonary hypertension). The importance of capillaroscopy is not only its diagnostic value but also its predictive value with its consequent implications in the follow-up and management of systemic sclerosis.

Behcet’s disease (BD) is a multi-system inflammatory disorder characterized by a relapsing–remitting course. Several treatment modalities with different mechanisms of action have been evaluated for the treatment of BD. In this review, our goal is to review updated therapeutic options for BD in the light of recently published The European League Against Rheumatism (EULAR) recommendations. Behcet’s disease can be difficult to treat with conventional treatment requiring escalation of therapy. In recent years, treatment of BD has become more effective since the understanding of the pathogenesis led to the use of a wide spectrum of therapeutic agents. Data in biologics have substantially increased in BD with different organ involvements in the last decades and providing promising results, although randomized controlled trials are lacking. Behcet’s disease can affect multi-organ system therefore treatment should be determined based on the clinical presentation and organ involvement. Since there is a lack of randomized controlled trials, treatment options are usually based on expert consensus, case reports/series, and retrospective/prospective studies. As the development of biologic agents continues, it seems likely that understanding of their efficacy and safety will improve which may lead to a change in the management strategy and clinical outcomes of BD.

OBJECTIVES To compare the clinical outcomes of oligometastatic versus widely metastatic NPC patients. MATERIALS AND METHODS Retrospective review of 157 patients with metastatic NPC at a tertiary hospital was performed. Multivariate analysis was carried out to compare the overall and progression-free survival (OS and PFS) of these two cohorts of NPC patients. The number of organ involvement and discrete metastatic lesions associated with improved OS and PFS were ascertained. RESULTS Patients with oligometastatic NPC (single organ, less than six discrete metastatic lesions) had a better median OS than patients with widespread metastasis (24.8 versus 12.8 months, P

Scrub typhus is one of the leading causes of acute febrile illness in India. It is associated with rash and often an eschar, which responds dramatically to antibiotics. In some cases, it results in serious illness leading to multiple organ involvement and finally death. The various clinical manifestations of scrub typhus arise mainly due to systemic vasculitis, caused by direct effects of organism as well as exaggerated immune response. The disease course is often complicated, leading to mortality in the absence of treatment. Here, in this case series, we describe three cases depicting the typical manifestations which a patient of scrub typhus can present with highlighting the fact that high index of clinical suspicion is of utmost importance for this deadly disease.

Objectives Turkey remains among the countries where hydatid disease is endemic. In this study, it was aimed to determine the number of operations performed for the treatment of pulmonary hydatid disease in Turkey during 2014 and to present the distribution of these operations according to the different regions of the country. Materials and methods The Turkish Thoracic Society Thoracic Surgery Study Group connected with the thoracic surgeons in each city through telephone. A data set was sent by email. The age, sex, contact with animals that might be a risk of gaining the hydatid disease, the side of the disease, the type of surgical method, other organ involvement were recorded and collected from each data set to form the final data, and the results were evaluated. Turkey comprises of 81 cities that are grouped in seven different regions. The number of operations was calculated for each city and region to present the distribution. Results Overall, 101 centers from 81 cities were considered in the study. A total of 715 pulmonary hydatid cyst operations were performed in 690 patients during the study period. The most common operation technique was cystotomy and capitonnage through thoracotomy (76%). The highest incidence rate of operated patients was in the Eastern Anatolian Region (2.15 patients per 100 000 person-years). Conclusion Pulmonary hydatid disease still has a high incidence rate particularly in the southeast and east of Turkey, which are mainly rural areas and where stockbreeding is very common. Cystotomy and capitonnage is still the most common surgical method used to treat pulmonary hydatid cysts. Preventive methods should be performed strictly in these cities and regions to decrease the risk of infection.

Objective To evaluate choroidal thickness (CT), corneal parameters, and scleral thickness (ST) in patients with systemic sclerosis (SSc) and to determine their relationship with disease-related quality of life (QoL). Methods The study included 38 patients with SSc and 40 healthy controls. A detailed ocular examination was performed on all participants. Corneal parameters such as K1, K2, Km, corneal volume (CV), central corneal thickness (CCT), and ST at a distance of 1000, 2000, and 3000 mu m from the scleral spur were measured. CT was measured at five points, including the subfoveal area and the temporal and nasal points at radii of 750.0 and 1500.0 mu m. The scleroderma health assessment questionnaire (SHAQ) was administered to SSc patients to investigate the disease-related QoL. Results Individuals with SSc had thicker ST at all distances from the scleral spur (P=0.008, P=0.001, P=0.002, respectively). All corneal parameters were significantly lower in the SSc group than in the control group (P < 0.05). Moreover, SSc patients had significantly lower median CT at N750.0, N1500.0, T750.0, and T1500.0 points and thinner subfoveal CT than healthy controls (P < 0.05). There was a weak-moderate negative correlation between ST and the components of the SHAQ scale and SHAQ-global. Conclusion Despite not having ocular involvement, SSc patients had thicker ST but thinner CT and corneal parameters than healthy controls. This may indicate subclinical inflammation in patients with SSc. Only ST was affected by organ involvement and QoL among the ocular parameters.

Tattooing is an increasing trend among Western countries, with about 18% of the population undergoing the procedure once in their lifetime. The process looks simple; introduce exogenous pigment into the dermis layer of the skin, altering the skin color permanently. However, this simple procedure leads to several health issues and medical complications, both acute and chronic, and some are difficult to cure. Sarcoidosis is high on the list of severity involving almost all body organs. Multiple organ involvement makes this condition more difficult to treat. Lungs and lymphatics are the leading sites of involvement, followed by an inflammatory disease of the eye called uveitis. An additional problem is the limited confirmatory diagnostic tests and treatment options for sarcoidosis. Each patient must be considered unique based on their age, clinical presentation, and severity of involvement. Proper treatment must be tailored for better outcomes with minimum side effects and rapid cure. Here we describe two case reports of tattoo-associated sarcoidosis with severe uveitis successfully treated with mycophenolate mofetil.

Management includes ruling out alternate diagnoses, identifying occult/overt organ involvement, determining treatment, and recognizing worrisome features.

Chronic urticaria is a disease characterized by the appearance of weals, angioedema or both longer than 6 weeks. Degranulation of cutaneous or submucosal mast cells leads to release of mediators including histamine resulting in redness, swelling and itch. Because mast cells are widely distributed throughout the body, the question is why they are not activated systemically or does systemic activation occur without overt end organ dysfunction? We have conducted an exploratory literature search for reports that have evidence of organ-specific dysfunction in chronic urticaria that might justify prospective observational studies. This search revealed some evidence of systemic effects of chronic urticaria in cardiac, respiratory, gastrointestinal, central nervous and musculo-skeletal systems. The relevance of these findings needs to be further determined. However, they justify prospective studies in larger numbers of patients and at different stages of disease activity.

Introduction: Extra-pulmonary Tuberculosis (EPT) amounts to about forty percent (40%) of the total epidemiology of Tuberculosis (TB). Detailed data of various systems and organ involvement of EPT is the objective of this article. Materials and Methods: Data of the EPT were collected from Indian Journal of Tuberculosis (IJT) since 2010-2016 for a period of 7 years. Details of age, side of lesion, affected sex and immune status were recorded in an excel sheet. The data were analyzed using Microsoft Excel 2007, SPSS version 23 software. Results: Total cases reported were 428, between 3-84 years. Females (220) were affected more than the males (186); genders of 22 cases were not specified. Genitourinary system was predominantly affected by EPT (213cases). Patients aged between 21- 40 were affected in highest percentage (69.39%) versus genitourinary system with a significant p-value of 0.000. Females were affected by EPT more than males with predominant involvement of the left side with a significant p-value of 0.000. Conclusion: This study provides significant information about the EPT with respect to the number of cases reported in a specified period and their age, gender, most common side of the disease. This study also highlights the predominant system involved by EPT and also the affected rare organs like tongue, clavicle, conjunctiva and breast. Keywords: Extra-pulmonary tuberculosis, Systems involved, Rare organs.

A granulomatose com poliangiite (GPA), anteriormente chamada de granulomatose de Wegener, é uma vasculite necrotizante granulomatosa sistêmica, pauci-immune, que afeta predominantemente o trato respiratório superior, os pulmões e os rins. Os pacientes afetados por essa moléstia podem apresentar sintomas gerais e específicos do comprometimento respiratório alto ou pulmonar, renal, cutâneo ou de outros órgãos. O tratamento é realizado principalmente com drogas imunossupressoras e deve ser instituído o mais precocemente possível. Este relato descreve as características clínicas e laboratoriais e a evolução de paciente com GPA em acompanhamento ambulatorial.

Objective.To assess the presence of a systemic sclerosis (SSc) pattern on nailfold capillary microscopy (NCM) in patients with Raynaud phenomenon (RP) and to explore its association with abnormal pulmonary function tests (PFT).Methods.NCM patterns were assessed in 759 consecutive patients with RP. Patterns were classified as normal (n = 354), nonspecific (n = 159), or SSc pattern (n = 246). Abnormal PFT was defined as forced vital or diffusion capacity < 70%. Patients were classified as primary RP (n = 245), or secondary: no definite diagnosis (n = 391), SSc (n = 40), primary Sjögren syndrome (pSS; n = 30), systemic lupus erythematosus (SLE; n = 30), mixed connective tissue disease (MCTD; n = 7), rheumatoid arthritis (RA; n = 15).Results.An SSc pattern on NCM was frequently observed in most patients with a definite diagnosis: SSc (88%), pSS (33%), SLE (17%), MCTD (71%), and RA (13%). In patients without definite diagnosis, 17% had a normal NCM pattern, 35% nonspecific, and 48% SSc pattern. Abnormal PFT was more frequent in patients with an SSc pattern (35.9% vs 19.5%, p = 0.002), even when corrected for SSc diagnosis (p = 0.003). Absence of an SSc pattern had high negative predictive value (88%); positive predictive values were low.Conclusion.SSc pattern on NCM is common in patients with RP, and in those with connective tissue diseases other than SSc. It is associated with a higher prevalence of abnormal PFT, independent of the presence of an SSc diagnosis. Although these data need validation in a prospective setting, they underline the importance of NCM in RP and putative value to stratify the risk of pulmonary involvement in early stages of disease.

In systemic lupus erythematosus (SLE), dsDNA antibodies are associated with renal disease. Less is known about comorbidities in patients without dsDNA or other autoantibodies. Using an electronic health record (EHR) SLE cohort, we employed a phenome-wide association study (PheWAS) that scans across billing codes to compare comorbidities in SLE patients with and without autoantibodies. We used our validated algorithm to identify SLE subjects. Autoantibody status was defined as ever positive for dsDNA, RNP, Smith, SSA and SSB. PheWAS was performed in antibody positive vs. negative SLE patients adjusting for age and race and using a false discovery rate of 0.05. We identified 1097 SLE subjects. In the PheWAS of dsDNA positive vs. negative subjects, dsDNA positive subjects were more likely to have nephritis ( p = 2.33 × 10−9) and renal failure ( p = 1.85 × 10−5). After adjusting for sex, race, age and other autoantibodies, dsDNA was independently associated with nephritis and chronic kidney disease. Those patients negative for dsDNA, RNP, SSA and SSB negative subjects were all more likely to have billing codes for sleep, pain and mood disorders. PheWAS uncovered a hierarchy within SLE-specific autoantibodies with dsDNA having the greatest impact on major organ involvement.

El lupus eritematoso sistémico (LES) es una enfermedad compleja y altamente heterogénea que afecta múltiples órganos, incluyendo articulaciones, corazón, sistema hematopoyético, sistema nervioso y riñón, siendo este último el de peor pronóstico y el que conlleva a nefritis lúpica (NL). Aunque la etiopatogénesis del LES aún no se conoce con claridad, se cree que la susceptibilidad genética y las modificaciones epigenéticas aberrantes favorecen su desenlace. Para establecer una terapia precisa es necesario evaluar de manera eficiente y objetiva el compromiso de órganos y la actividad de la enfermedad, lo cual es muy difícil por las pocas pruebas de laboratorio clínico disponibles en la actualidad. En las últimas décadas la búsqueda de nuevos biomarcadores de LES ha sido una tendencia y se han identificado varios promisorios a nivel de genómica, metabolómica, proteómica y transcriptómica. En esta revisión se resume el estado del arte relacionado con estudios transcriptómicos que han identificado diversos transcritos potencialmente útiles como biomarcadores del LES y la NL Systemic Lupus Erythematosus is a complex and highly heterogeneous disease affecting multiple organs such as joints, heart, hematopoietic system, nervous system and kidney, the latter being the worst prognosis and leading to lupus nephritis (LN). While the etiopathogenesis of SLE is still not completely clear, is believed that genetic susceptibility and aberrant epigenetic modifications favor the outcome of the disease. In order to establish an accurate therapy, it is necessary to efficiently and objectively assess organ involvement and disease activity, which is very dificult due to the clinical laboratory tests currently available. In recent decades, the search for new SLE biomarkers has been a trend and many promising biomarkers have been identified at the genomic, metabolomic, proteomic and transcriptomic levels. In this review we summarize the state of the art related to transcriptomic studies that have identified various potentially useful transcripts as biomarkers of SLE and NL. Systemic Lupus Erythematosus is a complex and highly heterogeneous disease affecting multiple organs such as joints, heart, hematopoietic system, nervous system and kidney, the latter being the worst prognosis and leading to lupus nephritis (LN). While the etiopathogenesis of SLE is still not completely clear, is believed that genetic susceptibility and aberrant epigenetic modifications favor the outcome of the disease. In order to establish an accurate therapy, it is necessary to efficiently and objectively assess organ involvement and disease activity, which is very dificult due to the clinical laboratory tests currently available. In recent decades, the search for new SLE biomarkers has been a trend and many promising biomarkers have been identified at the genomic, metabolomic, proteomic and transcriptomic levels. In this review we summarize the state of the art related to transcriptomic studies that have identified various potentially useful transcripts as biomarkers of SLE and NL.

Endothelial damage and fibro-proliferative vasculopathy of small vessels are pathological hallmarks of systemic sclerosis (SSc). The consequence is the detachment of resident elements that become circulating endothelial cells (CECs). The aim of our study was to evaluate the potential of CECs as biomarker in SSc. We enrolled 50 patients with limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) subset of SSc, who underwent clinical evaluation to establish the organ involvement. CECs were measured by flow-cytometry utilizing a polychromatic panel. An evident difference was observed in CEC counts comparing controls to SSc patients (median 10.5 vs. 152 cells/ml, p p

Background Type 1 autoimmune pancreatitis (AIP) is a pancreatic manifestation of IgG4-related disease (IgG4-RD). Although AIP and IgG4-RD are characterized by multiple organ involvement including salivary glands, lung, and kidney, co-occurrence of chronic rhinosinusitis (CRS) and AIP/IgG4-RD has been poorly defined. Objective We explored molecular mechanism accounting for the co-occurrence of CRS and AIP/IgG4-RD. Methods Serum concentrations of IFN-α and IL-33 were measured by enzyme-linked immune-sorbent assay. Results We encountered a patient with concurrent type 1 AIP/IgG4-RD and CRS. Induction of remission by prednisolone (PSL) for type 1 AIP/IgG4-RD led to a marked improvement of CRS. Serum cytokine analysis after PSL treatment revealed a marked reduction in serum concentrations of IFN-α and IL-33, both of which are candidate pathogenic cytokines for AIP/IgG4-RD. Conclusions Given that IL-33 is shared as one of pathogenic cytokines by type 1 AIP/IgG4-RD and CRS, enhanced IL33 responses may cause concurrent type 1 AIP/IgG4-RD and CRS.

Made available in DSpace on 2022-04-29T08:29:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-04-01 Juvenile systemic sclerosis (JSSc) is a rare disease of childhood and currently no international consensus exists with regard to its assessment and treatment. This SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) initiative, based on expert opinion informed by the best available evidence, provides recommendations for the assessment and treatment of patients with JSSc with a view to improving their outcome. Experts focused attention not only on the skin assessment but also on the early signs of internal organ involvement whose proper treatment can significantly affect the long-term outcome. A score for disease severity is proposed in order to perform a structured assessment of outcome over time but a validation in a wider patient population is recommended. Finally, a stepwise treatment approach is proposed in order to unify the standard of care throughout Europe with the aim to reduce morbidity and mortality in this disease. Hamburger Zentrum für Kinder- und Jugendrheumatologie Schoen Clinic Department of Woman and Child Health University of Padova, Via Giustiniani 3 Hospital Sant Joan de Déu University of Barcelona Department of Allergy Rheumatology and Clinical Immunology University Children's Hospital Clinical and Academic Paediatric and Adolescent Rheumatology Unit Alder Hey Children's NHS Foundation Trust Rheumatology Women's and Children's Hospital University of Adelaide Rheumatology Children's Hospital Westmead Department of Pediatrics Semmelweis Hospital Department of Pediatrics Cerrahpasa Medical School Istanbul University-Cerrahpasa Pediatric Rheumatology Unit Instituto de Puericultura e Pediatria Martagão Gesteira Universidade Federal Do Rio de Janeiro Centre for Adolescent Rheumatology Institute of Child Health University College London Paediatric Immunology and Rheumatology Wilhelmina Children's Hospital Department of Paediatrics Faculdade de Medicina de Botucatu Department of Paediatric Rheumatology Wilhelmina Children's Hospital European Reference Network RITA Department of Paediatrics Faculdade de Medicina de Botucatu

Although scleroderma (systemic sclerosis; SSc) is often associated with major internal organ involvement, acute emergencies may occur either independently or in association with progression of existing organ involvement. Two case examples illustrate the complexity of acute management of these emergencies. The first case with cold reactive (anti-C3d) antibody with type 1 cryoglobulin associated with dysproteinaemic state with IgM paraprotein illustrates an uncommon important cause for a common manifestation of SSc that requires specific intervention in addition to vascular support. The second case illustrates the complexity of multiorgan disease contributing to progressive dyspnoea and the identification of dominant pathological process considered to be the critical driver of the current symptomatology with an appreciation that failure to act in a timely manner will lead to precipitous deterioration of potentially reversible component(s) of the disease process in addition to meticulous monitoring of response over time.

Background Systemic sclerosis (SSc) is a severe and highly heterogeneous disease. The modified Rodnan skin score (mRSS) is a widely used tool for the assessment of the extent and degree of skin thickness. This study aimed to identify the classes of patients with early similar skin thickening trajectories without any a priori assumptions and study their associations with organ involvement and survival. Methods From the French SSc national cohort, patients with a disease duration of less than 2 years at inclusion and with at least 2 mRSS available within the first 4 years of follow-up were enrolled. Classes of patients with similar mRSS trajectories were identified based on a latent class mixed model. The clinical characteristics and survival rate were compared between the obtained classes. Results A total of 198 patients fulfilled the inclusion criteria, with a total of 641 mRSS available. The median disease duration and follow-up were 0.8 (interquartile range 0.4; 1.2) and 6.3 (3.8; 8.9) years, respectively. Individual trajectories of mRSS were highly heterogeneous between patients. Models with 1–6 latent classes of trajectories were sequentially assessed, and the 5-class model represented the best fit to data. Each class was characterized by a unique global trajectory of mRSS. The median disease duration did not differ significantly between classes. Baseline organ involvement was more frequent in classes with significant change over time (classes 2–5) than in class 1 (low baseline mRSS without significant change over time). Using Cox regression, we observed a progressively increasing risk of death from classes 1 to 5. Conclusions Early identification of clinical phenotype based on skin thickening trajectories could predict morbi-mortality in SSc. This study suggested that mRSS trajectories characterization might be pivotal for clinical practice and future trial designs.

Systemic lupus erythematosus (SLE) is an autoimmune disease mediated predominantly by immune complexes [1, 2]. A large number of autoantibodies against the component of the cell nuclei with a wide range of organ involvement is the hallmark of this disease [1, 3]. Multiple systemic involvements are a feature of this disease. Glomerulonephritis, dermatitis, arthritis, neurologic and hematologic involvement are the common manifestations [1, 3]. Ocular involvement is also common in SLE patients [1, 3, 4].

A 46-year-old male presented with a 12-month history of trichiasis and was found to have significant, progressive cicatrization of the tarsal conjunctiva causing entropion of the upper and lower eyelids. A biopsy confirmed the diagnosis of IgG4-related cicatrizing conjunctivitis in the absence of any other organ involvement, a previously unreported manifestation of this immune-mediated disease.

Sjögren’s syndrome is an autoimmune lymphocytic infiltrative disease that leads to chronic inflammatory and degradatory changes to exocrine glands and extra-glandular systemic organs. It rarely affects children and adolescents. In cases where adolescents are affected, a paucity of sicca symptoms, xerostomia, and xerophthalmia often leads to a missed diagnosis. Consequently, the first presenting sign of Sjögren’s syndrome in adolescents may be heterogeneous, with varying clinical symptoms related to parotitis or systemic organ involvement. In this case report, we discuss a 19-year-old girl with distal renal tubular acidosis (RTA), who had experienced severe hypokalemic episodes since the age of 14 years; the patient was eventually diagnosed with Sjögren’s syndrome. She was managed and maintained on potassium and alkali repletion therapy.

Systemic sclerosis (SSc) is a heterogeneous disease with variability in autoantibody profiles, skin and internal organ involvement, disease trajectory, and survival. The ability to identify more homogeneous subsets of SSc patients has informed patient care and been an essential aspect of SSc research. In this article, the historic evolution of subsetting systems in SSc are described including clinically based SSc subsetting systems, their utility, strengths, and limitations. There is a shifting paradigm of SSc subsets, including biologic classification of SSc subsets and fully data-driven approaches to SSc subset classification, taking into consideration the needs of the SSc global community in the modern era and the ability to prognosticate patients with SSc.

Objective: Little is known on the disease course of very early systemic sclerosis (SSc). Among the information yet to be elucidated is whether anticentromere antibody (ACA) isotype levels can serve as biomarkers for future SSc development and for organ involvement. This study was undertaken to evaluate whether IgG, IgM, and IgA ACA levels in IgG ACA–positive patients are associated with disease severity and/or progression from very early SSc to definite SSc. Methods: IgG ACA–positive patients from 5 different cohorts who had very early SSc or SSc fulfilling the American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) 2013 criteria were included. A diagnosis of very early SSc was based on the presence of IgG ACAs and Raynaud’s phenomenon, and/or puffy fingers and/or abnormal nailfold capillaroscopy, but not fulfilling the ACR/EULAR 2013 criteria for SSc. Multivariable regression analyses were performed to determine the association between baseline ACA isotype levels and progression to definite SSc with organ involvement. Results: Six hundred twenty-five IgG ACA–positive patients were included, of whom 138 (22%) fulfilled the criteria for very early SSc and 487 (78%) had definite SSc. Levels of IgG ACAs (odds ratio 2.5 [95% confidence interval 1.8–3.7]) and IgM ACAs (odds ratio 1.8 [95% confidence interval 1.3–2.3]) were significantly higher in patients with definite SSc. Of 115 patients with very early SSc with follow-up, progression to definite SSc occurred within 5 years in 48 (42%). Progression to definite SSc was associated with higher IgG ACA levels at baseline (odds ratio 4.3 [95% confidence interval 1.7–10.7]). Conclusion: ACA isotype levels may serve as biomarkers to identify patients with very early SSc who are at risk for disease progression to definite SSc.

Systemic sclerosis (SSc) is a connective tissue disease characterized by diffuse microangiopathy and immune dysregulation which ultimately result in widespread fibrosis of skin and internal organs. Although the 2013 EULAR/ACR criteria have allowed to improve the sensitivity for SSc diagnosis, it has recently come to light that the traditional subclassification into limited and diffuse cutaneous forms does not appear to fully capture the different phenotypes of the scleroderma spectrum. In this regard, a recent large cluster analysis-based study and other ongoing projects are trying to achieve a better stratification of SSc patients, as the disease course remains largely unpredictable to date. Recent preclinical studies and randomized controlled trials have yielded encouraging results with new drugs targeting inflammatory/immunological and fibrotic pathways. One of the main unmet needs in SSc remains the early identification of patients at high mortality risk, for whom aggressiveness of therapies ought to be determined and weighed against disease prognosis. Furthermore, lung and cardiac transplantation may also be taken into account in some carefully selected patients. Though the prognosis of SSc remains poor, an optimized stratification of patients along with the recent and ongoing advances in therapies could greatly impact the natural course of the disease in the near future. Moreover, it is envisioned that there will be an increasing need in the future to further develop combination therapies to better fight against this complex disease. In this review we discussed new insights into organ involvements and therapeutic options.

Systemic lupus erythematosus is a chronic autoimmune disease with various clinical manifestations, organ involvement and laboratory findings. The disease can involve any organ including skin, joints, kidneys, central and peripheral nervous system, cardiovascular system and more. Currently, the cornerstone of treatment includes antimalarial and immunosuppressive medications and glucocorticosteroids. Recently, great effort has been invested in finding more targeted drugs for achieving better control of the disease with less adverse events. Intravenous belimumab was the first and only biologic drug to be approved by the US FDA and Health Canada for lupus over the last 50 years, and recently was studied in subcutaneous form. This paper will review the major belimumab trials with a focus on the subcutaneous form.

Acquired autoimmune thrombotic thrombocytopenic purpura (TTP)-the most common form of TTP-is a life-threatening hematologic disease characterized by hemolytic anemia and thrombocytopenia. Acquired autoimmune TTP can cause signs and symptoms of neurologic and other organ involvement, with mortality approaching 90% if the disease is not promptly recognized and treated. Since the introduction of plasma exchange in 1991, the acquired autoimmune TTP survival rate has increased to 78%.

Adult-onset Still’s disease (AOSD) is a rare, systemic, inflammatory disorder characterized by spiking fevers, an evanescent eruption, arthritis, and multiorgan involvement. The disease has been recently classified as a polygenic autoinflammatory disorder at the “crossroads” of autoinflammatory and autoimmune diseases. The highly characteristic salmon-colored eruption is a cutaneous manifestation of a generalized inflammatory reaction and an important diagnostic criterion. In addition to the evanescent eruption, there are atypical persistent papules and plaques in many patients with AOSD. Emerging data suggest that AOSD with this typical evanescent eruption has a different clinicopathologic presentation and clinical course than AODS with atypical cutaneous manifestations. It appears that there are two subtypes of AOSD with different immunologic profiles, including (1) a systemic disease with high fever, organ involvement, and elevated levels of ferritin, and (2) a chronic disease course with arthritis as the predominant finding. These observations provide novel insight into the disease pathogenesis, suggesting that the underlying mechanisms might differ between these two forms, partially explaining the reported differences in drug response. Recent advances in the understanding of AOSD are summarized with a focus on the spectrum of cutaneous manifestations and its relationship to systemic inflammation.

The early diagnosis of systemic sclerosis (SSc) can be very difficult, when most of the typical signs and symptoms are absent. For this reason, the approach to SSc has changed during the last decades because the importance of an early diagnosis and treatment has been widely understood. "Very early SSc" is identified as a condition characterized by Raynaud's phenomenon, puffy fingers, disease-specific autoantibodies, and microvascular alterations at capillaroscopy. However, reliable biomarkers able to predict the disease evolution are missing, and decision whether to treat or not to treat in the earliest phase of the disease remains a dilemma. Presently, the only feasible clinical strategy in very early SSc remains a tight follow-up program to detect in "real time" the onset of internal organ involvement, which may thus allow an aggressive therapeutic agenda.

Introduction: Juvenile systemic sclerosis is an orphan disease. Currently, the majority of juvenile systemic sclerosis cohort studies are retrospective in design without standardized assessment. This study was conducted prospectively to investigate the difference in manifestations of limited cutaneous juvenile systemic sclerosis and diffuse cutaneous juvenile systemic sclerosis subtypes. An additional aim was to compare these data to other juvenile systemic sclerosis cohorts and a large adult systemic sclerosis cohort. Methods: Patients fulfilling the Paediatric Rheumatology European Society juvenile systemic sclerosis classification criteria were included. Clinical characteristics and patient-related outcomes were assessed. Results: In all, 88 patients with a mean disease duration of 3.5 years were enrolled, 72.5% with diffuse cutaneous juvenile systemic sclerosis with a mean modified Rodnan Skin score of 18 and 27.5% with limited cutaneous juvenile systemic sclerosis with mean modified Rodnan Skin score of 9. The mean age at the onset of Raynaud’s and first non-Raynaud’s symptoms was similar in both groups, approximately 9 and 10.5 years. Active digital tip ulcerations were present in 29% diffuse cutaneous juvenile systemic sclerosis and none in the limited cutaneous juvenile systemic sclerosis subjects (p = 0.005). Of those with cardiopulmonary testing, 3% of diffuse cutaneous juvenile systemic sclerosis and 23% of limited cutaneous juvenile systemic sclerosis group had cardiac involvement (p = 0.015), and 41% diffuse cutaneous juvenile systemic sclerosis and 22% of the limited cutaneous juvenile systemic sclerosis group had pulmonary involvement (p = 0.009). Physician global disease damage assessment was higher in the diffuse cutaneous juvenile systemic sclerosis group compared to the limited cutaneous juvenile systemic sclerosis group: 35 and 15 (p = 0.021). Discussion: The majority of this international juvenile systemic sclerosis cohort had diffuse cutaneous juvenile systemic sclerosis (72.5%) with more frequent vascular and pulmonary involvement compared to the limited cutaneous group, who had increased cardiac involvement. Our cohort reflects prior findings of published juvenile systemic sclerosis cohorts and emphasizes a difference in the presentation compared to adult-onset systemic sclerosis.

Behcet’s syndrome (BS) may cause several serious morbidities and a fatal outcome. A 20-year follow-up study found an overall mortality rate of 5–10% and increased standardized mortality ratios among young males. Major causes of death were large vessel and parenchymal central nervous system involvement. Mortality rate tends to decrease with time. The same trend is observed in the severity of eye disease and the frequency of skin–mucosa lesions. However, parenchymal CNS disease and peripheral artery aneurysms may occur late during the disease course. Also, male patients with BS are more prone to develop serious morbidities at long term even when they have no major organ involvement during the early years of their disease. Major morbidity results from eye, vascular, and neurological involvement. The outcome of eye disease is improving significantly with biological agents. However, still about 10% of patients may become blind despite treatment. Similarly, prognosis is still grim for pulmonary artery aneurysms, which lead to death in about one fourth of the affected cases, and parenchymal neurological involvement, which results in death or severe disability in approximately half of the affected cases. Here we review several aspects of morbidity and mortality due to BS.

Aim Identifying early clinical and biological factors associated with severe forms of postdiarrheal hemolytic uremic syndrome (D + HUS) that may help practitioners determine appropriate treatment. Methods This retrospective study was conducted in 49 children with D + HUS between 2001 and 2011. Severe forms were defined as occurrence of one of the following conditions: death, major neurological involvement, cardiovascular involvement, and/or the presence of sequelae (neurological, cardiovascular, pancreatic, or renal). Results During the acute phase, 35 children exhibited at least one type of extrarenal involvement including 13 severe forms with a median delayed occurrence after admission of 4.5 days (range: 1–8) for comatose children and 5 days (range: 2–6) for cardiovascular involvement; 32 children required dialysis and three died. In multivariate analysis, (i) major neurological involvement (n = 13), (ii) dialysis (n = 32), and (iii) sequelae (n = 12) were associated with (i) fever during the prodromal phase requiring dialysis at admission, (ii) C-reactive protein level (CRP) > 22 mg/L at admission, and (iii) major neurological involvement and a white blood cell count (WBC) > 20 × 103/mm3 during the acute stage, respectively. Conclusions D + HUS is a multiorgan disease with a delayed occurrence of life-threatening extrarenal organ involvement. Severe forms appear to be associated with early biological and clinical inflammatory parameters.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by erosive arthritis and systemic organ involvement. The disease may affect all ages and both sexes; usually it is seen in young women aged 25-45. Recent studies have shown that RA is among the most common inflammatory disease in older age groups. While elderly-onset rheumatoid arthritis (EORA) is still discussed in the literature, it is generally accepted as a disease beginning after 65 years of age. Compared with young-onset rheumatoid arthritis (YORA), it was found that EORA had different characteristics. EORA is characterized by more equal gender distribution, higher frequency of acute onset with constitutional symptoms, more frequent involvement of large joints, and lower frequency of rheumatoid factor (RF) positivity. Earlier diagnosis, less erosive disease and less disease-modifying antirheumatic drug usage were reported as distinguishing EORA from YORA patients. These various clinical presentations may cause difficulties in diagnosis and differential diagnosis of EORA. However, different clinical and treatment approaches may be needed in these patients. In this article, the clinical and laboratory characteristics, prognosis and treatment principles of EORA will be discussed in light of recent literature data. WOS:000417721900001 29290762 Q1