Drug Triggers and Clinic of Acute Generalized Exanthematous Pustulosis (AGEP): A Literature Case Series of 297 Patients

Acute generalized exanthematous pustulosis (AGEP) is a rare skin reaction, commonly caused by drugs. Available evidence mostly relies on small studies or case reports. We collected published AGEP case reports and, subsequently, described the patient characteristics, suspect and concomitant drugs, time to onset, disease management, and clinical prognosis. This study included 297 AGEP patients (64.3% women) obtained from 250 published case reports or case series with individual patient data. AGEP affected patients of all ages, but the majority of patients (88.2%) were ≥25 years old. The most frequently reported suspect drugs were anti-infectives for systemic use (36.5%), particularly antibacterials for systemic use (31.0%), and especially beta-lactam antibacterials (18.3%) and macrolides (4.3%). Other frequent suspect drugs were antineoplastics (12.2%), and anti-inflammatory/anti-rheumatic products (5.2%) plus hydroxychloroquine (12.8%). Mean time to onset was 9.1 days (standard deviation SD 13.94). Some patients developed fever (64.3%) and systemic involvement (18.9%), and most patients (76.4%) received pharmacological treatment for AGEP. Seven patients died, although five of them were already critically ill prior to AGEP. In conclusion, antibiotics remain the most common suspected cause of AGEP. While case mortality rate may be up to 2.5%, disentangling the role of AGEP on the fatal outcome from the role of the preexisting health conditions remains challenging.

Conjunctival lymphangiectasia and retinal angiopathy in hereditary transthyretin amyloidosis

Background Hereditary transthyretin amyloidosis (ATTR amyloidosis) is a rare condition where a mutation in the transthyretin gene leads to systemic deposition of amyloid. The manifestations and prognosis of ATTR amyloidosis depends on the specific ATTR mutation, with over 100 mutations reported in the literature. The manifestations of many rare forms of ATTR amyloidosis have not been well described, particularly the late-onset ophthalmic findings. Case presentation We present the case of a 43-year-old Caucasian male with a diagnosis of ATTRD18E amyloidosis confirmed by fat pad biopsy. He had diffuse systemic involvement, including cardiovascular, pulmonary, and gastrointestinal symptoms. He also had significant ocular involvement including vitreous opacities, retinal angiopathy, and conjunctival lymphangiectasia. These ocular findings modestly progressed at 2-year follow-up. Discussion The ATTRD18E mutation is a rare variant, with few described cases. To our knowledge, this is the first documented case of ATTRD18E amyloidosis with significant ocular involvement. These ocular findings may serve as a relevant biomarker for severe disease prognosis in ATTRD18E amyloidosis. With improving treatments addressing the systemic symptoms of ATTR amyloidosis, a better understanding of the late-onset ocular symptoms is becoming increasingly relevant.

Vasculopathy in COVID-19

COVID-19 is a primary respiratory illness that is frequently complicated by systemic involvement of the vasculature. Vascular involvement leads to an array of complications ranging from thrombosis to pulmonary edema secondary to loss of barrier function. This review will address the vasculopathy of COVID-19 with a focus on the role of the endothelium in orchestrating the systemic response to SARS-CoV-2 infection. The endothelial receptor systems and molecular pathways activated in the setting of COVID-19 and the consequences of these inflammatory and prothrombotic changes on endothelial cell function will be discussed. The sequelae of COVID-19 vascular involvement at the level of organ systems will also be addressed, with an emphasis on the pulmonary vasculature, but with consideration of effects on other vascular beds. The dramatic changes in endothelial phenotypes associated with COVID-19 has enabled the identification of biomarkers that could help guide therapy and predict outcomes. Knowledge of vascular pathogenesis in COVID-19 has also informed therapeutic approaches that may control its systemic sequelae. Since our understanding of vascular response in COVID-19 continues to evolve, we will consider areas of controversy, such as the extent to which SARS-CoV-2 directly infects endothelium and the degree to which vascular responses to SARS-CoV-2 are unique or common to those of other viruses capable of causing severe respiratory disease. This conceptual framework describing how SARS-CoV-2 infection affects endothelial inflammation, prothrombotic transformation, and barrier dysfunction will provide a context for interpreting new information as it arises addressing the vascular complications of COVID-19.

Evaluation of Oxidative Stress Biomarkers in Patients with Henoch-Schönlein Purpura

Introduction: Henoch-Schönlein Purpura (HSP) is a systemic vasculitic syndrome characterized by non-thrombocytopenic purpura, arthritis/arthralgia, abdominal pain, and glomerulonephritis. The pathogenesis of HSP has not been clearly identified. Oxidative damage has a role in the pathogenesis of most cases. Aim: This study aimed to evaluate changes of oxidative stress by studying parameters like superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) in an attempt to identify the role of oxidative stress in HSP from another perspective. Materials and methods: This study enrolled 23 pediatric patients (ten girls and thirteen boys) diagnosed with HSP who were under follow-up at Sutcu Imam University School of Medicine Department of Pediatrics between 2014 and 2016 and twenty healthy children as the control group. The parents of all subjects gave informed consent to participate in the study. In the HSP group, the beginning season of the illness and the systemic involvement during follow-up were determined. Blood specimens were obtained at presentation before any treatment was started. SOD, CAT activities, and MDA values in erythrocyte and plasma samples were compared between the patient group and the healthy children. Results: Twenty-three patients with HSP (13 males, 10 females) and 20 healthy children participated in this study. The mean age of the HSP cases was 8.21±3.78 years (range 2-16 years) and of the controls was 8.6±4.2 (range 3-14 years). The mean MDA value was 2.95±0.71 nmol/ml in the patient group and 2.67±0.66 nmol/ml in the control group (p=0.787). The mean level of the CAT enzyme was 1.32±0.35 U/g Hb in the patient group and 7.8±1.74 U/g Hb in the control group (p=0.001). The mean levels of the SOD enzyme were 3.06±0.85 U/g Hb in the patient group and 0.97±0.36 U/g Hb in the control group (p=0.001). Conclusions: Although high MDA levels support the role of lipid peroxidation in the pathogenesis of HSP, statistical significance was not reached owing to a limited number of our patients. The reduced CAT enzyme activity is consistent with the findings of previous reports. This finding supports the notion that oxidative stress can play a role in the pathogenesis of HSP. Keypoints: Our findings support the notion that oxidative stress can play a role in the pathogenesis of HSP.

Human Being in the Dimension of the Psychosociocultural Matrix of Philosophizing

Purpose. The article highlights the demand for critical thinking in everyday life at the present stage of development of globalized culture and emphasizes the role of philosophy as a source of rationality. Philosophizing, which is determined by the psychosociocultural matrix, sets the toposes, vocabulary and rhythms of meaning making, their preservation and transformation. The purpose of the article is to concretize the practices of socio-cultural communication, primarily through the social institute of education, where individuals interact with the psychosociocultural matrix of philosophizing, which mediate the general and individual level in philosophical culture. Theoretical basis of the study are cultural anthropology and phenomenological methods. Originality of the study: based on the philosophy of intersubjectivity, we actualized the rational grounds for formation of adequate judgments in modern culture at the level of everyday life. This justifies the inevitability of the spread of various forms and types of philosophical education, philosophical thinking, ideas and values developed in philosophical communities beyond the narrow circle of professional philosophers. This implies the systemic involvement of philosophers as professionals of meaning-making in solving problems in various non-academic fields – politics, economics, law, etc. The formation of skills of philosophical critical thinking in the process of preparing young people for active civil life is no less important aspect of this. Conclusions lead to an understanding of the existential importance of philosophy and philosophizing and the need for organized forms of knowledge transfer such as the Faculty of Philosophy of the Classical University. There is a mutual interest and interaction of the general culture of society and philosophy as a special kind of culture. Because philosophy actively configures other forms of culture, contributes to the creation of sociocultural identities precisely because of its ability to conceptually reproduce the core of the psychosociocultural matrix that underlies the existence of all these different forms within one society. The sociocultural macro level of philosophical spiritual practices is formed by the psychosociocultural matrix of the philosophical tradition, which retains its longevity from the emergence of philosophy and goes through its history, demonstrating the features of the national reception of philosophy as a national-specific embodiment of sociocultural macro level of the psychosociocultural matrix.

Autoimmune Polyglandular Syndrome Type II presenting as Subacute Combined Degeneration of Spinal Cord: A Neuroendocrinology Crossroad

Introduction - Autoimmune polyglandular syndrome (APS) is a condition having multiple endocrine abnormalities. It is divided into three types depending on the involvement of various endocrinopathies. It is also associated with other systemic involvement. The basic pathophysiology of this syndrome revolves around autoimmunity. Case Presentation - We present a 50 year old gentleman who presented to us in emergency with subacute onset progressive weakness of both lower limbs followed by upper limbs. On examination, patient was confused and disoriented. General examination findings include hypotension, pallor, facial puffiness and vitiligo. Neurological examination revealed spasticity and motor weakness in all four limbs with extensor planter response. Sensory examination during hospital course revealed posterior column involvement. Laboratory and radiological investigations confirmed subacute combined degeneration of spinal cord secondary to pernicious anaemia, Addison’s disease and autoimmune thyroid disease. The final diagnosis of autoimmune polyglandular syndrome type II was made after fulfilment of the required criteria. Conclusion – Autoimmune polyglandular syndrome type II can rarely present to neurologist as subacute combined degeneration of spinal cord. This syndrome and its systemic association should be kept in mind in order to reach the final diagnosis.

Resources of modern radiation diagnostics of sarcoidosis (review)

Introduction. Sarcoidosis is a significant social and medical problem. Diagnosis is based on consistency of the clinical picture, histological evidence of granulomatous inflammation, exclusion of alternative diseases, and evidence of systemic involvement. There is no “gold” diagnostic standard for sarcoidosis. Aim. Review of the latest world literature data on the possibilities of modern radiation diagnosis of sarcoidosis. Materials and methods. The review summarizes data from literature published mainly over the past five years in PubMed and eLibrary. Earlier publications were also included as necessary. Results. In the literature review, modern medical imaging methods used to diagnose sarcoidosis, which in some cases can avoid biopsy, are considered. First of all, these are X-ray methods. Today, high-resolution multispiral computed tomography with three-dimensional imaging, as the method with the highest sensitivity, plays a decisive role in the diagnosis and monitoring of sarcoidosis. The use of magnetic resonance imaging and low-dose computed tomography is not well understood in patients with sarcoidosis. Quantitative computed tomography and radiomics techniques have only been partially tested in sarcoidosis. Conclusion. The imaging of sarcoidosis is the subject of a large number of publications that provide detailed descriptions of X-ray and computed tomography techniques. Nevertheless, despite the introduction of new computerized tools for the analysis of chest imaging, traditional X-ray techniques still remain an important role in both the diagnostic and prognostic assessment of changes characteristic of sarcoidosis

Phacomatosis pigmentovascularis with sturge-weber syndrome and congenital glaucoma: A rare case report

Phacomatosis pigmentovascularis (PPV) is a rare congenital disease characterized by the co-existence of cutaneous vascular malformation and pigmentary nevi with or without extracutaneous systemic involvement. Here, we present a 2-month old child diagnosed with phacomatosis cesioflammea type of PPV with Sturge-Weber syndrome and secondary congenital glaucoma of the left eye. She underwent combined trabeculotomy and trabeculectomy in the left eye for glaucoma and was started on anti-epileptics for seizure control following pediatric evaluation. Early screening and treatment initiation can prevent blindness and other systemic complications associated with PPV.

Squamous Cell Carcinoma Complicating Plaque of Lupus Erythematosus - A Case Series

Lupus Erythematosus is a multisystem disorder with a wide spectrum of clinical presentations ranging from cutaneous involvement to widespread systemic involvement. Squamous cell carcinoma formation in cutaneous lesions of LE is rare but had greater chances of metastases. Here, we report two cases, one of Discoid Lupus Erythematosus and other of Systemic Lupus Erythematosus complicated by development of squamous cell carcinoma over cutaneous lesions.

Redefining WILD syndrome: a primary lymphatic dysplasia with congenital multisegmental lymphoedema, cutaneous lymphovascular malformation, CD4 lymphopaenia and warts

BackgroundPrimary lymphoedema (PL) syndromes are increasingly recognised as presentations of complex genetic disease, with at least 20 identified causative genes. Recognition of clinical patterns is key to diagnosis, research and therapeutics. The defining criteria for one such clinical syndrome, ‘WILD syndrome’ (Warts, Immunodeficiency, Lymphoedema and anogenital Dysplasia), have previously depended on a single case report.Methods and resultsWe present 21 patients (including the first described case) with similar clinical and immunological phenotypes. All had PL affecting multiple segments, with systemic involvement (intestinal lymphangiectasia/pleural or pericardial effusions) in 70% (n=14/20). Most (n=20, 95%) had a distinctive cutaneous lymphovascular malformation on the upper anterior chest wall. Some (n=10, 48%) also had hyperpigmented lesions resembling epidermal naevi (but probably lymphatic in origin). Warts were common (n=17, 81%) and often refractory. In contrast to the previous case report, anogenital dysplasia was uncommon—only found in two further cases (total n=3, 14%). Low CD4 counts and CD4:CD8 ratios typified the syndrome (17 of 19, 89%), but monocyte counts were universally normal, unlike GATA2 deficiency.ConclusionWILD syndrome is a previously unrecognised, underdiagnosed generalised PL syndrome. Based on this case series, we redefine WILD as ‘Warts, Immunodeficiency, andLymphatic Dysplasia’ and suggest specific diagnostic criteria. The essential criterion is congenital multisegmental PL in a ‘mosaic’ distribution. The major diagnostic features are recurrent warts, cutaneous lymphovascular malformations, systemic involvement (lymphatic dysplasia), genital swelling and CD4 lymphopaenia with normal monocyte counts. The absence of family history suggests a sporadic condition, and the random distribution of swelling implicates mosaic postzygotic mutation as the cause.