Analysis of the pathogenic factors and management of dry eye in ocular surface disorders

The tear film represents the interface between the eye and the environment. The alteration of the delicate balance that regulates the secretion and distribution of the tear film determines the dry eye (DE) syndrome. Despite having a multifactorial origin, the main risk factors are female gender and advanced age. Likewise, morphological changes in several glands and in the chemical composition of their secretions, such as proteins, mucins, lipidics, aqueous tears, and salinity, are highly relevant factors that maintain a steady ocular surface. Another key factor of recurrence and onset of the disease is the presence of local and/or systemic inflammation that involves the ocular surface. DE syndrome is one of the most commonly encountered diseases in clinical practice, and many other causes related to daily life and the increase in average life expectancy will contribute to its onset. This review will consider the disorders of the ocular surface that give rise to such a widespread pathology. At the end, the most recent therapeutic options for the management of DE will be briefly discussed according to the specific underlying pathology

Cranial Neuralgias in Children and Adolescents A review of the literature

Cranial neuralgias are a well-established cause of headache-related morbidity in the adult population. These disorders are poorly studied in general due to their relative rarity, particularly in children and adolescents, and they are likely underdiagnosed in these populations. Recognizing these disorders and differentiating them from more common headache disorders, such as migraine, is important, as secondary disease is common. This review will cover the basic epidemiology, diagnosis, and treatment of trigeminal, occipital, glossopharyngeal and other, less common, cranial neuralgias. We have reviewed pediatric case reports of these conditions. For trigeminal neuralgia, the most common of these disorders, we have compiled the clinical features and treatment response of previous reports

SJS/TEN 2019: From Science to Translation

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs

SJS/TEN 2019: From science to translation.

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care needs

Updates in SJS/TEN: collaboration, innovation, and community

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is a predominantly drug-induced disease, with a mortality rate of 15–20%, that engages the expertise of multiple disciplines: dermatology, allergy, immunology, clinical pharmacology, burn surgery, ophthalmology, urogynecology, and psychiatry. SJS/TEN has an incidence of 1–5/million persons per year in the United States, with even higher rates globally. One of the challenges of SJS/TEN has been developing the research infrastructure and coordination to answer questions capable of transforming clinical care and leading to improved patient outcomes. SJS/TEN 2021, the third research meeting of its kind, was held as a virtual meeting on August 28–29, 2021. The meeting brought together 428 international scientists, in addition to a community of 140 SJS/TEN survivors and family members. The goal of the meeting was to brainstorm strategies to support the continued growth of an international SJS/TEN research network, bridging science and the community. The community workshop section of the meeting focused on eight primary themes: mental health, eye care, SJS/TEN in children, non-drug induced SJS/TEN, long-term health complications, new advances in mechanisms and basic science, managing long-term scarring, considerations for skin of color, and COVID-19 vaccines. The meeting featured several important updates and identified areas of unmet research and clinical need that will be highlighted in this white paper

Update on Fever of Unknown Origin in Children: Focus on Etiologies and Clinical Approach

Fever of unknown origin (FUO) can be caused by four etiological categories of diseases. The most common cause of FUO in children is represented by infections, followed by inflammatory conditions and neoplastic causes; a decreasing quote remains still without diagnosis. Despite the fact that several diagnostic and therapeutic approaches have been proposed since the first definition of FUO, none of them has been fully validated in pediatric populations. A focused review of the patient’s history and a thorough physical examination may offer helpful hints in suggesting a likely diagnosis. The diagnostic algorithm should proceed sequentially, and invasive testing should be performed only in select cases, possibly targeted by a diagnostic suspect. Pioneering serum biomarkers have been developed and validated; however, they are still far from becoming part of routine clinical practice. Novel noninvasive imaging techniques have shown promising diagnostic accuracy; however, their positioning in the diagnostic algorithm of pediatric FUO is still not clear. This narrative review aims to provide a synopsis of the existent literature on FUO in children, with its major causes and possible diagnostic workup, to help the clinician tackle the complex spectrum of pediatric FUO in everyday clinical practice

A pilot study of serum granulysin in drug induced exanthems and severe cutaneous adverse reactions (SCARs)

OBJECTIVES: 1. To measure serum granulysin levels and study its relationship with disease severity in patients with drug induced exanthems and severe cutaneous adverse reactions. 2. To study the clinical and cutaneous profile of patients with drug induced exanthems and severe cutaneous adverse reactions. METHODS: A prospective case-control study was conducted for a period of 19 months. Twenty two cases of maculopapular exanthema and twenty one cases of severe cutaneous adverse reactions were recruited. Twenty age-matched healthy volunteers were also enrolled as controls. Naranjo adverse drug reaction probability scale was used to determine causality. A detailed history was taken and examination was conducted. The serum granulsyin was measured with Biovendor RD191327200R Human Granulysin ELISA, a sandwich-enzyme linked immunosorbent assay. The data entry was performed using Epidata software and analysis by using SPSS software. The independent sample t test was used for the comparison of normally distributed variables. RESULTS: The mean age of the patients was 44.4 ± 14.6 years. There was a female preponderance with M : F 0.41:1. Aromatic anticonvulsants were the most commonly implicated drug group (35.4%). Facial oedema and peripheral eosinophilia among patients with MPE and SCARs were comparable (p – 0.929, >0.99 respectively). Transaminitis was significantly more common in SCARs than MPE (p value 0.021). Dermal eosinophilia was the most common histopathological feature in CADRs (83.3%). Necrotic keratinocytes and lymphocytic exocytosis were significantly more common in SCARs than MPE (p – 0.01, 0.045 respectively). There was no significant difference in serum granulysin between patients with MPE, SCARs and healthy controls. Granulysin titer was significantly higher in patients with SJS/TEN than in patients with erythema multiforme major (0.275 ng/ml vs 0.125 ng/ml, p value – 0.042)

Urticarial Syndromes

Urticaria is a common dermatological condition that can occur in acute and chronic forms. Common urticaria is generally easy to diagnose; however, urticarial syndromes should be considered in cases where lesions persist for greater than 24–36 h, the location of lesions has bilateral symmetry, urticarial lesions are accompanied by additional elementary lesions, and/or the patient presents with additional systemic symptoms. Additionally, urticarial syndromes should be considered for patients with typical urticarial lesions that do not respond to systemic antihistamine treatment. Hyperpigmentation or bruising can be observed following resolution of urticarial syndromes. Many cutaneous and systemic diseases can cause urticarial syndromes. Systemic causes of urticarial syndromes can affect multiple organ systems and may be accompanied by systemic symptoms such as fever, asthenia, and arthralgia. Clinicopathologic correlation is essential for the accurate diagnosis of urticarial syndromes. In this chapter, cutaneous and systemic etiologies of urticarial syndromes are reviewed

Viral infections in immunosuppressed patients with hematological malignancies

Acute or reactivated viral infections are common in patients who are immunosuppressed because of hematopoietic stem cell transplantation (HSCT) or chemotherapy due to hematological malignancies. The severity of the immunosuppression, the type of immune functions that are affected by various therapeutic interventions, as well as underlying hematological malignancy contributes to viral susceptibility and clinical outcome of the infection. Furthermore, in patients undergoing HSCT, the serostatus of viruses with reactivation capacity in both the recipient and the donor must be considered, as well as the sociodemographic and genetic characteristics. Here we have studied DNA viruses that can cause clinical events in patients with malignant hematological diseases. Foremost, we evaluated whether it is advisable to continuously screen for the presence of these viruses during illness or chemotherapy in children and adults. In papers I and II we studied the presence of human adenovirus (HAdV) in the blood of patients undergoing HSCT. In papers III and IV, the presence of parvovirus B19 (B19V) in the bone marrow of children with various malignancies was studied, while paper V focused on the presence of B19V in the blood of adults and children undergoing HSCT. Paper VI focused on human herpesvirus 6 (HHV-6), polyoma BK virus (BKV) and B19V in the blood of adult patients undergoing chemotherapy for non-transplanted hematological malignancies. In these retrospective studies, blood and/or bone marrow samples were analyzed by quantitative real-time PCR for DNA representing HAdV, B19V, HHV-6 and BKV. Clinical and laboratory data were obtained from medical records. The proportion of patients with HAdV infection was relatively small, and asymptomatic infections did not occur. On the other hand, HAdV DNA loads >15,000 copies/mL in blood were associated with morbidity and mortality. Furthermore, findings of B19V in bone marrow of children undergoing treatment for acute lymphoblastic leukemia (ALL), were associated with prolonged chemotherapy. Neither B19V, HHV-6A, 6B nor BKV was common in the blood of adult patients with hematological malignancies who were immunosuppressed due to chemotherapy. In general, screening for these viruses in the patient groups presented may not be indicated at the current state. However, testing for HAdV should be performed generously when unexpected symptoms occur, even if they are not typical for the virus. B19V infection is almost always linked with some degree of cytopenia, and if unexpected cytopenia occurs in children undergoing chemotherapy, B19V infection should be tested for. Patients with primary infections normally suffer from more severe clinical disease as compared to those with reactivated infections. Thus, knowledge of viral serostatus in HSCT recipients and donors should be taken into account in diagnostic considerations. Overall, the diagnostic value of direct viral detection in blood and/or bone marrow samples of immunosuppressed patients with hematological malignancies is of considerable importance. Hopefully, a broad spectrum of novel antiviral compounds as well as novel procedures for adoptive cell therapy will be developed for these viral infections. Whether novel interventions will be used as pre-emptive therapy, or as symptomatic treatment, there will be an urgent need to monitor viral load. The present thesis can thus inform the field of clinically relevant viral infections and how to monitor these in selected patient categories that can be targeted for future therapeutic clinical interventions