Case Report: Eosinophilic Bronchiolitis With Eosinophil ETosis in Mucus Plugs Successfully Treated With Benralizumab

Eosinophilic bronchiolitis is a rare allergic disorder caused by eosinophilic inflammation in the bronchioles of the lungs. An effective treatment strategy is needed in cases resistant to steroids. However, its pathophysiology remains unclear owing to the limited number of cases. We herein present the case of a 31-year-old man who experienced eosinophilic bronchiolitis with eosinophil ETosis (EETosis) in the mucus plugs. The patient was diagnosed with asthma. His respiratory symptoms worsened with eosinophilia when treated with the standard asthma regimen, including inhaled corticosteroids, long-acting β2-agonist, long-acting muscarinic antagonist, and leukotriene receptor antagonist. Chest computed tomography revealed bronchial wall thickening and centrilobular nodules in the lower lobes of both lungs. Bronchoscopy showed obstruction of the subsegmental bronchus with mucus plugs. Histological analysis demonstrated abundant eosinophils in the mucus plugs. Cytolytic eosinophils together with Charcot–Leyden crystal formations and deposition of major basic proteins were also observed, indicating the occurrence of EETosis. Introduction of benralizumab, an anti-interleukin-5 receptor α antibody, successfully controlled the patient’s condition and reduced the amount of systemic corticosteroids administered. Our findings confirm that this antibody strongly decreases airway eosinophils in patients with severe asthma. Thus, benralizumab might be an optimal therapeutic agent for the treatment of mucus plug-forming and/or EETosis-occurring eosinophilic lung diseases, including eosinophilic bronchiolitis.

Central nervous system infections in patients with systemic lupus erythematosus: a systematic review and meta-analysis

We aimed to conduct a systematic review and meta-analysis of studies on central nervous system (CNS) infections in patients with SLE, in order to describe their clinical and microbiological characteristics, and outcomes. A systematic search of PubMed/Medline and Embase electronic databases was performed (March 2021) to identify all published studies on CNS infections and their characteristics in patients with SLE. A random-effects model was adopted and findings were reported with 95% CI. Overall, 6 studies involving 17 751 patients with SLE and 209 SLE cases with CNS infection were included in our meta-analysis. The frequency rate of CNS infections in patients with SLE was 0.012 (95% CI: 0.008 to 0.018). Meningitis was the most common clinical syndrome (93.5%, n=109/114, 95% CI: 82.6% to 97.8%) and Cryptococcus neoformans (35.9%, n=55, 95% CI: 27.2% to 45.7%) and Mycobacterium tuberculosis (27.1%, n=43, 95% CI: 14.6% to 44.8%) were the most common causative pathogens. Our patient-pool showed a mean SLE Disease Activity Index (SLEDAI) score of 7.9 (95% CI: 6.1 to 9.6), while 92.4% (n=72/76, 95% CI: 83.0% to 96.8%) of cases were on oral systemic corticosteroids, with a prednisone equivalent mean daily dose of 30.9 mg/day (95% CI: 18.0 to 43.7). Our meta-analysis revealed a mortality rate of 29.0% (95% CI: 15.0% to 48.6%). Clinicians should maintain a high index of suspicion for cryptococcal and tuberculosis (TB) meningitis in patients with SLE with suspected CNS infection, particularly in those with higher SLEDAI and on higher doses of systemic corticosteroids. In conclusion, initiation of empiric antituberculous treatment for patients with SLE who are highly suspected to have CNS TB is warranted while awaiting the results of diagnostic tests. Antifungals might also be potentially useful empirically in patients with SLE who are suspected to have fungal CNS infections. However, with respect to side effects such as toxicity and high cost of antifungals, decision regarding early antifungal therapy should be guided by early and less time-consuming fungal diagnostic tests.

Delayed allergic skin reactions to vaccines

Background: Recent advances in vaccination against the severe acute respiratory syndrome coronavirus 2 pandemic have brought allergists and dermatologists to the forefront because both immediate and delayed hypersensitivity reactions have been reported. Objective: This literature review focused on delayed reactions to vaccines, including possible causative agents and practical information on how to diagnose, evaluate with patch testing, and manage subsequent dose administration. Methods: Currently published reviews and case reports in PubMed, along with data on vaccines from the Centers for Disease Control and Prevention web site. Relevant case reports and reviews that focused on delayed reactions to vaccines were selected. Results: Most delayed hypersensitivity reactions to vaccines include cutaneous manifestations, which vary from local persistent pruritic nodules to systemic rashes. The onset is usually within a few days but can be delayed by weeks. Multiple excipients have been identified that have been implicated in delayed vaccine reactions, including thimerosal, formaldehyde, aluminum, antibiotics, and gelatin. Treatment with antihistamines, topical corticosteroids, or systemic corticosteroids alleviates symptoms in most patients. Such reactions are generally not contraindications to future vaccination. However, for more-severe reactions, patch testing for causative agents can be used to aid in diagnosis and approach further vaccination. Conclusion: Delayed-type hypersensitivity reactions to vaccines are not uncommon. If needed, patch testing can be used to confirm agents, including antibiotics, formaldehyde, thimerosal, and aluminum. In most cases, delayed cutaneous reactions are not contraindications to further vaccine administration.

Necrotizing Anterior Scleritis in a Woman with Terrien’s Marginal Degeneration: A Case Report

Purpose: The aim of the study was to report the first case of a patient with Terrien’s Marginal Degeneration (TMD) who developed necrotizing anterior scleritis without systemic disease association, requiring systemic immunosuppressive treatment. Case Report: A 32-year-old female consulted for bilateral ocular burning and hyperemia. Initially, she was diagnosed with conjunctivitis and treated with topical antibiotics and corticosteroids, with mild transitory improvement but the progression of the disease. Years later, she attended the ocular immunology consultation for a second opinion where TMD with ocular inflammatory component OU was diagnosed. Seven months later, she presented with severe pain, decreased visual acuity, and photophobia in OS. At the slit-lamp examination, necrotizing anterior scleritis with a high risk of perforation in OS was observed. The patient was referred to the rheumatologist and started treatment with systemic corticosteroids and cyclophosphamide, exhibiting a clinical improvement. The patient did not meet the criteria for any systemic illness associated with scleritis, such as autoimmune diseases or vasculitis. Thus, scleritis was related to the adjacent inflammatory process associated with TMD, as an atypical presentation of this disease. Conclusion: Although an inflammatory type of TMD has been proposed, it is essential to follow up closely these patients and consider necrotizing anterior scleritis, a severe ocular disease that requires prompt immunosuppressive management, as a possible atypical associated presentation of this disease.

A Commentary on the “Duration of Oral Antibiotics Administration for Cetuximab-Induced Acneiform Eruption”

Acneiform eruption is a devastating cutaneous side effect of cetuximab, a monoclonal antibody used to treat a variety of cancers. Despite its effectiveness, many patients avoid or discontinue it after experiencing its dermatological side effects as it negatively impacts their quality of life (QoL). This displays the immense need for multidisciplinary collaboration to prevent and treat cetuximab-induced acneiform eruption (CIAE). Prevention methods include, but are not limited to, education, skin care routines, and prophylactic drugs. The following measures reduce the likelihood of developing CIAE and decrease its severity, making it easier to treat if it were to occur. Ongoing research on the treatment of CIAE continues. Of these treatments, oral tetracyclines and systemic corticosteroids have been shown to be the most effective by far. This commentary aims to evaluate the study by Park et al. [Dermatology. 2021;237(3):457–63], further elaborate on prevention and treatment measures of CIAE, and highlight the implications of CIAE on a patient’s QoL.

Purpura Fulminans in a 20-Year-Old Female

A previously healthy 20-year-old female presented with extensive retiform purpura located at the face, upper and lower limbs, one week after an episode of acute tonsillitis. Despite the exuberance of the cutaneous findings and progression to skin necrosis she had no accompanying symptoms. Laboratory investigation revealed a heterozygous protein C mutation (exon 9, c.1332G> C, p.Trp444Cys), accounting for a partial deficiency of this anticoagulant protein. The patient was started on broad spectrum antibiotics, anticoagulation and systemic corticosteroids, with no lesional progression and complete resolution of cutaneous ulceration within 6 months. This is a singular case of purpura fulminans, since two different causative factors precipitated the events. The previous tonsillitis reported by the patient is significant, because the serum concentration of protein S may also decrease after an infectious event - post-infectious purpura fulminans. This case illustrates that purpura fulminans due to autoantibodies against protein S, although rare, should be considered, especially in the absence of a severe acute infection. It also illustrates how in a given patient different independent factors can act simultaneously, triggering potentially devastating clinical scenarios.

Anti-Inflammatory Effects of Immunostimulation in Patients with COVID-19 Pneumonia

Background: The effects of immunomodulators in patients with Coronavirus Disease 2019 (COVID-19) pneumonia are still unknown. We investigated the cellular inflammatory and molecular changes in response to standard-of-care + pidotimod (PDT) and explored the possible association with blood biomarkers of disease severity. Methods: Clinical characteristics and outcomes, neutrophil-to-lymphocyte ratio (NLR), plasma and cell supernatant chemokines, and gene expression patterns after SARS-CoV-2 and influenza (FLU) virus in vitro stimulation were assessed in 16 patients with mild-moderate COVID-19 pneumonia, treated with standard of care and PDT 800 mg twice daily (PDT group), and measured at admission, 7 (T1), and 12 (T2) days after therapy initiation. Clinical outcomes and NLR were compared with age-matched historical controls not exposed to PDT. Results: Hospital stay, in-hospital mortality, and intubation rate did not differ between groups. At T1, NLR was 2.9 (1.7–4.6) in the PDT group and 5.5 (3.4–7.1) in controls (p = 0.037). In the PDT group, eotaxin and IL-4 plasma concentrations progressively increased (p < 0.05). Upon SARS-CoV-2 and FLU-specific stimulation, IFN-γ was upregulated (p < 0.05), while at genetic transcription level, Pathogen Recognition Receptors (TRLs) were upregulated, especially in FLU-stimulated conditions. Conclusions: Immunomodulation exerted by PDT and systemic corticosteroids may foster a restoration in the innate response to the viral infection. These results should be confirmed in larger RCTs.