Toxic epidermal necrolysis as a result of chlorthalidone and cyclophosphamide combination

Case report Introduction: Toxic epidermal necrolysis (TEN), is an immune-mediated disease characterized by severe mucocutaneous symptoms and is the result of an inflammatory response that leads to keratinocyte necrosis and perivascular lymphocyte infiltration, mostly drug-related. Case report: A 35-year- old male, with a history of recently diagnosed systemic lupus under treatment with prednisone, hydroxychloroquine, mycophenolate and cotrimoxazole forte evolves with persistent proteinuria, it is decided to add losartan, chlorthalidone and atorvastatin. Nevertheless despite immunosuppression, proteinuria and skin involvement persisted, so mycophenolate was suspended and a bolus of cyclophosphamide 1 g was administered. Eight weeks after adjusting treatment, the patient went to the emergency department due to a confluent, pruritic, maculopapular rash with blistering lesions on the trunk, upper limbs, face, and oral mucosa, associated with fever over 38degreeC, that evolved during one week. On admission, the following was confirmed: confluent erythematous macular exanthem associated with multiple flaccid blisters on the chest, upper limbs and neck, Nikolsky's sign (+), keratoconjunctivitis and dryness on the lips. Admission tests included complete blood count with no leukocytosis or eosinophilia, ESR 29 mm/hr, C-RP 19.8 mg/L, no liver profile abnormalities, creatinine 0.8 mg/dl, and urine test with proteinuria 300 mg/dl. Negative infectious study for mycoplasma, herpes 6 virus, cytomegalovirus, Epstein barr virus, hepatitis A, B, C, E and SARS-COV2 virus. Due to severe mucosal skin involvement, TEN/SJS was suspected v/s (TEN)-like Lupus presentation, drugs used prior to admission (chlorthalidone, losartan, atorvastatin) were discontinued, and treatment was started with Hydrocortisone 100 mg every 8 hours IV, Immunoglobulin 2 g/kg daily IV for 4 days, plus skin and mucous membrane care. Patient had a favorable evolution, with resolution of skin and mucosal lesions and no signs of infection. Skin biopsy showed necrotic epidermis, necrotic basal keratinocytes, and sparse lymphocytic inflammatory infiltrate in the papillary dermis, consistent with erythema multiforme/toxic epidermal necrolysis. Conclusion(s): Extensive mucosal involvement is one of the cardinal signs of the presentation of SJS/ETN and given its severity, a high index of suspicion is important with the consequent suspension of suspected drugs and support management for a favorable evolution. In this case the suspected culprit drug was the combination of cyclophosphamide and chlorthalidone, due to reports of increased toxicity of cyclophosphamide in combination with diuretic drugs.

The effect of COVID-19 imposed lockdown on Italian children with Vernal Keratoconjunctivitis.

Background: Vernal keratoconjunctivitis (VKC) is a chronic, inflammatory-allergic disease of the cornea and conjunctiva. Environmental factors, such as light exposure, have been supposed to play a role in the pathogenesis of ocular inflammation and in the worsening of VKC. Objective: The aim of this study was to estimate the impact of reduced sunlight exposure in patients with VKC during the imposed lockdown period for the SARS-CoV-2 pandemic emergency. Methods: We retrospectively reviewed data of patients with VKC visited during spring season in 2020 and 2019 at Vernal Keratoconjunctivitis Multidisciplinar Outpatient of our Hospital.Subjective symptoms were evaluated by Visual analogue scale (VAS) and VKC severity was graded by Bonini scale. Quality of life was evaluated by Correlations of Quality of Life in Children with Vernal Keratoconjunctivitis (QUICK) questionnaire. The number of hours of e-learning as well as of hours spent in front of a bright screen (PC, TV, mobile, tablet play station, and so on) was also investigated. Results: Twenty-nine male subjects (mean ± SD age: 8.74 ± 2.40 years) with VKC were included in the study. Most of the patients (17/29) were sensitized individuals.No significant changes in Bonini severity score and in VAS evaluation were observed comparing 2020 to 2019 values. Ten (34.4%) patients did benefit from the reduced sunlight exposure. The increased use of bright screens was associated with worsening of VKC severity. Conclusions: Sunlight exposure plays a role in VKC exacerbation in about one third of patients. The number of hours spent in front of bright screens may influence severity of VKC symptoms.

Unboxing herpes zoster ophthalmicus and the recombinant shingles vaccine

Reactivation of the varicella zoster virus as herpes zoster (shingles) typically affects the peripheral nerves, resulting in a painful rash, most often on the torso. However, it can also manifest ophthalmologically, affecting the ophthalmic division of the trigeminal nerve. This manifestation is associated with a particularly high level of morbidity and may result in blindness. A new recombinant shingles herpes zoster vaccine protects patients against this virus and post-infection sequelae, improving medical and psychosocial outcomes. © 2021 Medicine Today Pty Ltd. All rights reserved.

Impact of screen exposure on pediatric vernal Keratoconjunctivitis: a survey during the COVID-19 pandemic in Italy.

BACKGROUND: The SARS-CoV-2 outbreak pushed the Italian government to start a strict lockdown, replacing school attendance with long-distance learning. This caused reduced exposure to sunlight but increased exposure to screens. Vernal keratoconjunctivitis (VKC) is a chronic inflammatory ocular condition in which exposure to light plays a cardinal role. We conducted an online survey to evaluate the impact of screen exposure on children with VKC during the COVID-19 lockdown. METHODS: We performed a survey-based observational study, asking patients followed at the Allergology clinics of Meyer Children's University Hospital in Florence and of Policlinico Umberto I in Rome to provide grading on 6 subjective ocular clinical manifestations presented during the lockdown and to give an estimate of their hours/day of screen exposure. RESULTS: Mean scores of signs and symptoms increased homogeneously when studying patients exposed to longer screen time. When comparing scores collected in 2019 to those in 2020, there was not a significant reduction in clinical manifestations, although the situation differed between the two centers due to geographical differences in sunlight exposure. CONCLUSION: During the lockdown, there was a reduction in sunlight exposure but conversely an increase in the time spent in front of screens that correlated with the worsening of VKC signs and symptoms in direct proportion to the hours/day of screen exposure. Our results also showed a statistically significant difference in the relative impact of long-distance learning on VKC clinical manifestations in the different Italian regions.

Impact of Social Distancing and Personal Hygiene on the Prevalence of Epidemic Keratoconjunctivitis during the COVID-19 Pandemic

Purpose: To analyze the change in the weekly incidence of epidemic keratoconjunctivitis (EKC) per 1,000 outpatients during the coronavirus disease 2019 (COVID-19) pandemic by comparing the mean weekly proportion of EKC of 2020 with that from 2016 to 2019. Methods: Using data from the Korea Disease Control and Prevention Agency for 2016-2020, we analyzed the weekly proportion of EKC per 1,000 outpatients. The data were also analyzed according to age, semester and vacation periods, region, and social distancing stages. For the Daegu data, we also analyzed the effects of social distancing in an area. Results: The mean weekly proportion of EKC per 1,000 outpatients in 2020 was lower than in previous years for all ages (2016-2019 19.77 ± 7.17 , 2020 7.28 ± 2.97 ;p 0.001). During the semester, the mean difference between 2016-2019 and 2020 was significant, particularly for preschool children. In Daegu, the weekly proportion of EKC per 1,000 outpatients during the extra 12-18 weeks of social distancing was significantly lower (2016-2019, 18.78 ± 6.61 ;2020, 8.94 ± 2.92 ;p 0.001). Conclusions: The public health interventions implemented during the COVID-19 outbreak not only reduced the prevalence of COVID-19 but also reduced the prevalence of EKC. Therefore, maintaining hygiene principles and standard precautions may help prevent EKC. © 2022 Korean Ophthalmological Society (KOS). All rights reserved.

Ocular Surface Infection by SARS-CoV-2 in COVID-19 Pneumonia Patients Admitted to Sub-Intensive Unit: Preliminary Results.

The aim of the present study is to check the relationship between virus detection on the conjunctival swabs by RT-PCR and the systemic and ocular clinical data, treatments, and to the modalities of administration of supplemental oxygen. The SARS-CoV-2 RNA reverse-transcriptase PCR assay of conjunctival brushing samples and the corneal/conjunctival clinical findings were evaluated in 18 eyes of 9 consecutive patients admitted to the COVID-19 Sub-intensive Unit of Salerno Hospital University, Italy. Conjunctival swabs were positive for SARS-CoV-2 in 13 eyes of 7 patients; corneal epithelial defects were detected in 9 eyes. The seven patients with ocular involvement from SARS-CoV-2 had undergone treatment with a full-face mask or oxygen helmet in the last week, while the two subjects with negative conjunctival swabs had been treated with high flow nasal cannula. The positivity to the conjunctival test for SARS-CoV-2 was higher (72%) than that reported in the literature (10-15%) and related in all cases to the use of facial respiratory devices. These results suggest that exposure of unprotected eyes to aerosols containing high concentrations of SARS-CoV-2 could cause a keratoconjunctival viral infection. Further studies are needed to verify the causal link with the use of respiratory facial devices in patients suffering from COVID-19 pneumonia.

[Anterior eye segment damage in coronavirus infection (COVID-19)]. / Porazhenie perednego segmenta glaza pri koronavirusnoi infektsii (COVID-19).

Conjunctivitis may appear as the first symptom of the coronavirus infection (COVID-19). In isolated cases, the lesion of the conjunctiva evokes a systemic infectious process. Currently, the conjunctiva is not considered as an area of long-term reproduction of coronavirus, and its damage is caused by hyperproduction of pro-inflammatory cytokines (especially IL-6); development of iridocyclitis and keratoconjunctivitis is also possible. Most often, local corticosteroids are used to treat these processes, although their use requires caution due to the risk of activating secondary infection (herpetic bacterial, fungal), which often develops as a result of immunodeficiency caused both by COVID-19 and the massive corticosteroid and antibiotic therapy employed when the course of the disease is severe. The severe condition of patients, the lung ventilation, and the prone position all contribute to corneal erosions, exposure keratopathy, pseudomonas aeruginosa keratitis and angle-closure glaucoma attacks. The risk of transmission of coronavirus infection during keratoplasty is estimated as minimal.

Portuguese immunoallergology clinical experience in patients with severe atopic dermatitis under dupilumab treatment

Background: Dupilumab has been recently approved for treatment in patients with severe AD in Portugal-until now there is no published data regarding Portuguese experience in Allergy centers. Method: Cross sectional clinical and laboratory assessment of 33 patients (pts) with moderate to severe AD treated with dupilumab (dupi) for at least 16 weeks (W): prospective evaluation of severity scores (SCORAD-Scoring Atopic Dermatitis, EASI-Eczema Area and Severity Index, P-VAS-Pruritus Visual Analogic Scale), report of adverse events up to 52 weeks of treatment. SCORAD and EASI were assessed in 23 pts at W52, P-VAS in 21 pts at W52. Results: Of the 33 pts, 18 were female (55%) with a mean age (SD, range) of 35.3 years (13.2, 15-60). In 16 pts the age of onset was before 2 years old, mean (SD) disease duration 28.1 years (12);94% patients had a diffuse pattern of skin lesions;97% of pts had allergic rhinitis, 82% asthma, 52% conjunctivitis and 30% food allergy. Median total IgE at baseline was of 6313 U/ml (P25-P75: 2842-12491) with a 76% reduction at W52 in 16 pts. Median eosinophil count at baseline was 520 eosinophils/mm3 (P25-P75: 270-740). Before starting dupi 29 pts had been treated with cyclosporine. At the beginning, 15 pts were under oral corticosteroids, 14 under oral systemic immunosuppressive drugs (all pts but two stopped both until W12 of dupi) and 5 switched from omalizumab. At baseline, median SCORAD and EASI were 69.3 and 24.2 points. At W16, W36 and W52, median SCORAD was 27.4, 22.3 and 21.5, and median EASI 5.3, 4.1 and 2.1. At W16, the EASI-50, EASI-75 and EASI-90 were achieved by 91%, 61% and 18% pts, and at W52, by 87%, 70% and 52% pts. The mean percentage of SCORAD reduction at W16 and W52 was 55% and 73%;and of EASI was 76% and 82%. At W16 and W52, an improvement of ≥4 points in P-VAS was achieved by 77% and 95% pts. There was a mean reduction of P-VAS at W2, W4, W16 and W52 of 2.6;3.6;4.7 and 6.3 points, respectively. Conjunctivitis was reported in 10 (30%) pts, two of them with keratoconjunctivitis and blepharitis, without needing to interrupt treatment;two pts also had facial erythema. One patient had COVID, and dupilumab scheme treatment was maintained. Conclusion: The majority of AD patients had a significant and consistent improvement in all the severity scores, after one year of treatment with dupilumab. No relevant adverse events were reported.

COVID-19 case presented initially with keratoconjunctivitis: A case report.

INTRODUCTION: Ocular complaints are considered non-classical presentations for COVID-19 infection; the initial diagnosis of keratoconjunctivitis is even rarer. Indeed, this puts treating clinicians in danger of getting infected, especially when patients present without the classic respiratory symptoms. CASE: Here we report a case of COVID-19 that was initially presented with keratoconjunctivitis with the appearance of respiratory symptoms four days later. The case showed improvement within four days of successful treatment for both covid pneumonia and ocular disease. DISCUSSION: Countable cases reported initial ocular symptoms to co-occur with systemic symptoms or even before. Only two cases reported the diagnosis of keratoconjunctivitis in COVID-19. The two cases differ in the proposed mechanism of developing such disorder. One by direct invasion of the virus, the other one by cytokines-induced epithelial injury. Our case did not show positivity for SARS-CoV 2 in the eye secretion, which aligns with the later proposed mechanism of pathology. CONCLUSION: It is crucial to report such cases to increase the awareness of atypical presentation for COVID-19 infection. This is too important for two reasons: first, to diagnose the disease itself, and second, to take infection control precautions when treating such cases, with unexpected initial presentation.

Bell's palsy after inactivated COVID-19 vaccination in a patient with history of recurrent Bell's palsy: A case report.

BACKGROUND: With rapid and extensive administration of inactivated coronavirus disease 2019 (COVID-19) vaccine to the general population in China, it is crucial for clinicians to recognize neurological complications or other side effects associated with COVID-19 vaccination. CASE SUMMARY: Here we report the first case of Bell's palsy after the first dose of inactivated COVID-19 vaccine in China. The patient was a 36-year-old woman with a past history of Bell's palsy. Two days after receiving the first dose of the Sinovac Life Sciences inactivated COVID-19 vaccine, the patient developed right-side Bell's palsy and binoculus keratoconjunctivitis. Prednisone, artificial tears and fluorometholone eye drops were applied. The patient's symptoms began to improve by day 7 and resolved by day 54. CONCLUSION: As mRNA COVID-19 vaccine trials reported cases of Bell's palsy as adverse events, we should pay attention to the occurrence of Bell's palsy after inactivated COVID-19 vaccination. A history of Bell's palsy, rapid increase of immunoglobulin M and immunoglobin G-specific antibodies to severe acute respiratory syndrome coronavirus 2 may be risk factors for Bell's palsy after COVID-19 vaccination.

Prolonged face mask use might worsen dry eye symptoms.

Purpose: The aim of this study was to explore whether prolonged and consistent face mask use might be associated with worsening of dry eye symptoms in patients with dry eye disease (DED). Methods: Subjects with a previous diagnosis of DED. Their OSDI scores were compared with those recorded in Fall 2019 using the Wilcoxon paired test. Participants were stratified by face mask use: heavy (Group A) or standard (Group B) face mask users. Heavy use was defined as wearing any type of face mask for at least 6 hours a day, at least 5 days per week in the last 2 months. Results: 67 subjects (mean age: 45.27 ± 10.06 SD years, 40% males and 60% females). Median OSDI score in Fall 2019: 18.75. Median OSDI in Spring 2020: 20.83. The Hodges-Lehmann median difference was 2.09 (95% CI [1.05, 4.17]) (P < 0.0001). The population was then stratified into heavy and standard face mask users: Group A included heavy users (31 subjects; mean age: 42.81 ± 10.48 SD years; 35% males and 65% females), Group B included standard users (36 subjects; mean age: 47.39 ± 9.31 SD years; 44% males and 56% females). The Hodges-Lehmann median difference was 5.21 (95% CI [3.13, 7.29]) in Group A (P < 0.0001), and 1.04 (95% [0],[ 2.08]) in Group B (P = 0.0177). Conclusion: Prolonged and consistent face mask use is associated with an increase in OSDI scores. Whether face mask use is responsible for the worsening of symptoms of DED remains to be elucidated.

Recurrent keratoconjunctivitis as the sole manifestation of COVID-19 infection: A case report.

INTRODUCTION: Ocular symptoms are uncommon manifestations of coronavirus disease 2019 (COVID-19) infection. Earlier study reported that dry eye, blurred vision, foreign body sensation, tearing, itching, conjunctival secretion, conjunctival congestion, ocular pain, and photophobia are among the ocular symptoms that could be found in COVID-19 patients. However, there are only a few reports available regarding corneal involvement in this disease. Here we report a case of keratoconjunctivitis as the only symptom of COVID-19 infection. CASE DESCRIPTION: A 27-year-old man who worked as an obstetrics and gynecology resident came to the outpatient clinic with the chief complaints of eye discomfort, foreign body sensation, conjunctival hyperemia, lacrimation, and photophobia in his right eye for the past 3 weeks. Fluorescence test showed a small corneal lesion. The patient was then diagnosed with keratoconjunctivitis. A week after the treatment, all symptoms were resolved. A month later, the patient came to the emergency room with the same eye complaints but with a more severe pain. The fluorescence test showed wider corneal lesion compared to last month. The result from the corneal swab is negative for bacterial or fungal infection, indicating a viral infection. Afterwards, reverse transcriptase polymerase chain reaction test from nasopharyngeal swab was performed and revealed that the patient was positive for COVID-19. CONCLUSIONS: This case report showed that keratoconjunctivitis may occur as the only manifestation of COVID-19 infection. Thus, patient presented with unexplainable eye symptoms should be evaluated for COVID-19 infection.

Systemic diseases and the cornea.

There is a number of systemic diseases affecting the cornea. These include endocrine disorders (diabetes, Graves' disease, Addison's disease, hyperparathyroidism), infections with viruses (SARS-CoV-2, herpes simplex, varicella zoster, HTLV-1, Epstein-Barr virus) and bacteria (tuberculosis, syphilis and Pseudomonas aeruginosa), autoimmune and inflammatory diseases (rheumatoid arthritis, Sjögren's syndrome, lupus erythematosus, gout, atopic and vernal keratoconjunctivitis, multiple sclerosis, granulomatosis with polyangiitis, sarcoidosis, Cogan's syndrome, immunobullous diseases), corneal deposit disorders (Wilson's disease, cystinosis, Fabry disease, Meretoja's syndrome, mucopolysaccharidosis, hyperlipoproteinemia), and genetic disorders (aniridia, Ehlers-Danlos syndromes, Marfan syndrome). Corneal manifestations often provide an insight to underlying systemic diseases and can act as the first indicator of an undiagnosed systemic condition. Routine eye exams can bring attention to potentially life-threatening illnesses. In this review, we provide a fairly detailed overview of the pathologic changes in the cornea described in various systemic diseases and also discuss underlying molecular mechanisms, as well as current and emerging treatments.

Epidemic Keratoconjunctivitis in India: Trend Analysis and Implications for Viral Outbreaks.

Purpose: To describe the correlation between the temporal pattern of presentation of acute epidemic keratoconjunctivitis (EKC) of presumed adenoviral etiology with meteorological parameters such as environmental temperature, rainfall, humidity, and wind speed. Methods: This cross-sectional hospital-based study included 2,408,819 patients presenting between August 2010 and February 2020. Patients with a clinical diagnosis of EKC in at least one eye were included as cases. A smaller cohort of patients with acute (≤1 week) presentation hailing from the district of Hyderabad during the calendar years 2016-2019 was used to perform correlation analysis with the local environmental temperature, rainfall, humidity, and wind speed (data obtained from the Telangana State Development and Planning Society). Results: Overall, 21,196 (0.87%) patients were diagnosed with EKC, of which 19,203 (90.6%) patients had acute onset; among which the cohort from the district of Hyderabad included 1,635 (8.51%) patients. The mean monthly prevalence in this cohort was 0.89% with a peak prevalence in April (1.09%). The environmental parameters of rainfall (r2 = 0.47/P = 0.0131), humidity (r2 = 0.65/P = 0.0014), and wind speed (r2 = 0.56/P = 0.0047) were significantly negatively correlated with the temporal pattern of EKC in the population. There was no visible trend or significant correlation seen with temperature (r2 = 0.08/P = 0.3793). Conclusion: Contrary to popular belief, epidemic viral infections like EKC may not be affected by temperature, but rather by a complex interplay of other environmental factors such as humidity, rainfall, and wind speed. An increase in rainfall, wind speed, and humidity contributes to a lower prevalence of EKC cases during the year.

COVID-19 and ocular implications: an update.

BACKGROUND: COronaVIrus Disease 19 (COVID-19) was first reported in Wuhan, China in December 2019 and is now pandemic all over the world. The purpose of this review is to highlight the possible ocular presentation of COVID-19 infection and the consequence of the pandemic in the daily ophthalmology routine. A total of 9 articles was included by searching PubMed database for articles published between December 2019 and April 2020. MAIN BODY: Conjunctivitis (and keratoconjunctivitis) can be the first symptom in infected patients. The virus can be present in tear and conjunctival secretions, requiring maximum attention. It's important to understand if COVID-19 could spread through the ocular route or present as the primary infected site. Ocular implications should also be considered for therapy. In fact, one potential treatment is chloroquine and its derivatives, including hydroxychloroquine. Hydroxychloroquine, in fact, can induced retinal toxicity. The exponential increase in lthe number of Covid-19 cases was like a tsunami for health care companies, which were not ready to face this emergency. Ophthalmology departments were also affected by the reorganization of healthcare services. CONCLUSION: The studies analaysed have some limitations. First, the sample size and the covered population consisted mainly of patients with mild disease. Moreover, the studies are often descriptive study, without a correlation analysis. Finally, no normal population was observed in the studies, so a normal control group should be included for comparison in future studies. With the evolving COVID-19 pandemic and with its high infectivity, it is necessary to rearrange ophthalmologist routine clinical practice in order to control viral spread and try to maximize patient and health-care provider's safety.