Baricitinib as a novel treatment for bullous pemphigoid: a case series report (preprint)

Bullous pemphigoid (BP) is an autoimmune blistering disorder occurring mostly in the elderly. The standard treatment of BP patients with systemic corticosteroid have some potential serious side effects. Up till now, there is still lack of novel treatment for BP patients. Baricitinib, a selective Janus kinase (JAK) 1 and 2 inhibitor, has been used to treat rheumatoid arthritis, alopecia areata, and COVID-19. Successful treatment of refractory BP by JAK inhibitors has been reported in sporadic cases. In this study, we reported 8 BP patients treated with baricitinib. The patients after treatment were followed up for 3-24 months, with an average of 9.1 months. All 8 cases achieved disease control and the mean disease control period was 3 weeks (1-6 weeks). The bullous pemphigoid disease area index total (21.2 ± 13.0 to 2.5 ± 4.3, p<0.01), erosion/blister (6.0 ± 7.7 to 0.2 ± 0.5, p<0.05), urticaria/erythema (10.2 ± 11.9 to 0.0 ± 0.0, p=0.06), mucosal erosion/blister (10.0 ± 6.4 to 4.5 ± 5.1, n=4, p=0.25) and itching NRS (3.6 ± 3.5 to 0.0 ± 0.0, p=0.06) scores were all reduced after 2 months’ treatment. Seven of 8 patients achieved complete remission during tapering at month 3 and did not experience relapse during the follow-up period. The serum levels of anti-BP180 autoantibodies (IgG) were reduced significantly (77.1 ± 47.8U/mL to 40.1 ± 37.1U/mL, n=6, p<0.05) after 3 months’ treatment. During the follow-up period, only one patient experienced mild elevation of serum creatinine level after 3 months’ treatment of baricitinib, which returned to normal through discontinuation of the medication. In conclusion, this study demonstrated that low-dose, short-term administration of baricitinib is effective and safe for treating BP patients.

COVID 19-associated chilblain-like acral lesions among children and adolescents: an Italian retrospective, multicenter study.

BACKGROUND: Since the COVID-19 pandemic started, great interest has been given to this disease, especially to its possible clinical presentations. Besides classical respiratory symptoms, dermatological manifestations occur quite often among infected and non-infected patients, particularly in children. A prominent IFN-I response, that is generally higher in children compared to adults, may not only cause chilblain lesions, but it could also prevent infection and viral replication, thus justifying the negative swab results, as well as the absence of relevant systemic symptoms in positive cases. Indeed, reports have emerged describing chilblain-like acral lesions in children and adolescents with either proven or suspected infection. METHODS: Patients aged from 1 to 18 years old were enrolled in this study from 23 Italian dermatological units and were observed for an overall period of 6 months. Clinical pictures were collected along with data on the location and duration of skin lesions, their association with concomitant local and systemic symptoms, presence of nail and/or mucosal involvement, as well as histological, laboratory and imaging findings. RESULTS: One hundred thirty-seven patients were included, of whom 56.9% were females. Mean age was 11.97±3.66 years. The most commonly affected sites were the feet (77 patients, 56.2%). Lesions (48.5%) featured cyanosis, chilblains, blisters, ecchymosis, bullae, erythema, edema, and papules. Concomitant skin manifestations included maculo-papular rashes (30%), unspecified rashes (25%), vesicular rashes (20%), erythema multiforme (10%), urticaria (10%) and erythema with desquamation (5%). Forty-one patients (29.9%) reported pruritus as the main symptom associated with chilblains, and 56 out of 137 patients also reported systemic symptoms such as respiratory symptoms (33.9%), fever (28%), intestinal (27%), headache (5.5%), asthenia (3.5%), and joint pain (2%). Associated comorbid conditions were observed in 9 patients presenting with skin lesions. Nasopharyngeal swabs turned out positive in 11 patients (8%), whereas the remainder were either negative (101, 73%) or unspecified (25, 18%). CONCLUSIONS: COVID-19 has been credited as the etiology of the recent increase in acro-ischemic lesions. The present study provides a description of pediatric cutaneous manifestations deemed to be potentially associated with COVID-19, revealing a possible association between acral cyanosis and nasopharyngeal swab positivity in children and teenagers. The identification and characterization of newly recognized patterns of skin involvement may aid physicians in diagnosing cases of asymptomatic or pauci-symptomatic COVID patients.

Sneddon-Wilkinson disease following COVID-19 vaccination.

Sneddon-Wilkinson disease, also known as subcorneal pustular dermatosis (SPD), is a rare disease characterized by vesicles or pustules that may rapidly expand and coalesce. Idiopathic in nature, SPD's clinical presentation of "half-half" blisters, with half of each blister containing pus and half containing clear fluid, is characteristic of this disease. We describe a previously healthy 21-year-old man who developed acute pustular vesicular eruptions consistent with SPD eight days following the Moderna COVID-19 vaccination.

Immunosuppressive treatment for autoimmune blistering diseases does not impair production of neutralizing antibodies after "booster" dose of COVID-19 vaccine.

Since vaccines against COVID-19 are available, it has been debated if immunosuppressed patients with autoimmune blistering diseases (AIBDs) should be advised to interrupt the immunosuppressive therapy before receiving the vaccine, with consequent risk to experience a flare of disease. In the present study, we measured the neutralizing antibodies production after anti-SARS-CoV-2 vaccination in patients with AIBDs on immunosuppressive treatment, compared to healthy controls. Our results give strength to the hypothesis that these patients do not need to discontinue their therapy to produce effective levels of neutralizing antibodies, in other words to achieve successful protection.

Cutaneous Manifestations in Patients with SARS-CoV-2 Infections.

While SARS-CoV-2 is known to cause pneumonia and acute respiratory distress syndrome (ARDS), many extrapulmonary manifestations of COVID-19 have also been observed. Cutaneous manifestations including erythematous rash, urticaria, and chickenpox-like vesicles have been described in patients with SARS-CoV-2. Six patients, two men and four women, in the age group of 50 to 60 years old, hospitalized with SARS-CoV-2 infection confirmed with real-time polymerase chain reaction (real-time PCR) presented cutaneous manifestations. The rash was confluent, spotty, centrifugal, and non-itchy on the head and torso. It was not hemorrhagic, and no crust or blisters were observed. The results of laboratory tests were normal, and the rash disappeared on its own. Several cases of cutaneous manifestations have been reported in patients with SARS-CoV-2 infection. Further studies are needed in order to assess the skin lesions and determine their association with COVID-19.

Vesiculobullous and Other Cutaneous Manifestations of COVID-19 Vaccines: a Scoping and Narrative Review.

As coronavirus disease (COVID-19) vaccines continue to be administered, dermatologists play a critical role in recognizing and treating the cutaneous manifestations (CM) associated with the vaccines. Adverse cutaneous reactions of COVID-19 vaccines reported in the literature range from common urticarial to rare vesiculobullous reactions. In this study, we performed a (1) scoping review to assess the occurrences of vesicular, papulovesicular, and bullous CMs of COVID-19 vaccines and their respective treatments, and (2) a narrative review discussing other common and uncommon CMs of COVID-19 vaccines. Thirty-six articles were included in the scoping review, and 66 articles in the narrative review. We found that vesicular, papulovesicular, and bullous lesions are infrequent, reported mostly after the first dose of Moderna or Pfizer vaccines. Eleven of the 36 studies reported vesicular reactions consistent with activation or reactivation of the herpes zoster virus. Most vesicular and bullous lesions were self-limited or treated with topical corticosteroids. Other CMs included injection-site, urticarial or morbilliform reactions, vasculitis, toxic epidermal necrolysis, and flaring of or new-onset skin diseases such as psoriasis. Treatments for CMs included topical or oral corticosteroids, antihistamines, or no treatment in self-limited cases. Although most CMs are benign and treatable, the data on the effect of systemic corticosteroids and immunosuppressive therapies on the immunogenicity of COVID-19 vaccines is limited. Some studies report reduced immunogenicity of the vaccines after high-dose corticosteroids use. Physicians may consult local guidelines where available when recommending COVID-19 vaccines to immunosuppressed patients, and when using corticosteroids to manage the CMs of COVID-19 vaccines.

Herpes Zoster Following COVID-19 Vaccine Booster.

BACKGROUND Herpes zoster is a condition in which there is reactivation of varicella zoster virus (VZV), which is usually seen in the elderly and those with immunocompromised states. Recently, however, there have been many reports of herpes zoster after administration of COVID-19 vaccines, although initial trials showed that these vaccines have good safety and immunogenicity profiles. At the time of writing, about 5 billion people worldwide had received their full course of COVID-19 vaccination. This case report describes an elderly man who developed herpes zoster after receiving a booster dose of the Pfizer-BioNTech (BNT162b2) vaccine, with no adverse effects after the first and second dose. CASE REPORT An 82-year-old man with underlying type 2 diabetes mellitus, hypertension, dyslipidemia, and cerebrovascular disease presented with left-sided chest and upper back pain. The pain was intermittent, burning in nature, and disturbed his sleep. A week prior to his presentation, he received a COVID-19 vaccine (BNT162b2) booster dose. Examination revealed multiple vesicles along his anterior and posterior T3 dermatome. He was diagnosed with herpes zoster and treated with a course of oral acyclovir. Upon review 7 days later, he had recovered well, with resolution of his vesicles and pain. CONCLUSIONS COVID-19 vaccination remains an important measure to prevent transmission of infection and to reduce the mortality and morbidity caused by it. However, healthcare practitioners should be aware of the possible association between COVID-19 vaccination and herpes zoster. Appropriate explanation and safety advice on the possible adverse events following COVID-19 vaccination, including herpes zoster infection, should be given to patients. This will facilitate early recognition and treatment of this condition.

A dermatologic assessment of 101 mpox (monkeypox) cases from 13 countries during the 2022 outbreak: Skin lesion morphology, clinical course, and scarring.

BACKGROUND: In the 2022 mpox (monkeypox) outbreak, 79,000 global cases have been reported. Yet, limited dermatologic data have been published regarding lesion morphology and progression. OBJECTIVE: The objective of this study was to characterize skin lesion morphology, symptomatology, and outcomes of mpox infection over time. METHODS: The American Academy of Dermatology/International League of Dermatological Societies Dermatology COVID-19, Mpox, and Emerging Infections Registry captured deidentified patient cases of mpox entered by health care professionals. RESULTS: From August 4 to November 13, 2022, 101 cases from 13 countries were entered, primarily by dermatologists (92%). Thirty-nine percent had fewer than 5 lesions. In 54% of cases, skin lesions were the first sign of infection. In the first 1-5 days of infection, papules (36%), vesicles (17%), and pustules (20%) predominated. By days 6-10, pustules (36%) were most common, followed by erosions/ulcers (27%) and crusts/scabs (24%). Crusts/scabs were the predominant morphology after day 11. Ten cases of morbilliform rash were reported. Scarring occurred in 13% of the cases. LIMITATIONS: Registry-reported data cannot address incidence. There is a potential reporting bias from the predilection to report cases with greater clinical severity. DISCUSSION: These findings highlight differences in skin findings compared to historical outbreaks, notably the presence of skin lesions prior to systemic symptoms and low overall lesion counts. Scarring emerged as a major possible sequela.

SARS-CoV-2 vaccine-triggered conversion from systemic lupus erythematosus (SLE) to bullous SLE and dipeptidyl peptidase 4 inhibitors-associated bullous pemphigoid.

Bullous systemic lupus erythematosus (BSLE) is a rare blistering disease in patients with SLE. BSLE is a heterogenous disease caused by autoantibodies to the basement membrane, mainly type VII collagen. The pathogenesis of the development of autoantibodies in BSLE remains unknown. We report a case of SLE taking dipeptidyl peptidase 4 inhibitors (DPP4i) who developed tense blister lesions after administration of SARS-CoV-2 vaccine. Initial erythematous lesion before administration of SARS-CoV-2 vaccine had not shown IgG deposition at basement membrane both direct and indirect immunofluorescence (IIF). However, the result of those examinations became positive after the administration of SARS-CoV-2 vaccine. Furthermore, IIF test results using NaCl split skin had shown positive against epidermal side. These observations suggest that SARS-CoV-2 vaccination triggered production of autoantibodies that cause bullous SLE. The present case fulfills the diagnostic criteria for both BSLE and DPP4i-associated bullous pemphigoid. Skin lesions were cleared after withdrawal of DPP4i. Therefore, physicians should ask patients who develop blisters after the vaccination whether they are taking DPP4i.

Mediastinal Emphysema, Giant Bulla, and Pneumothorax Developed during the Course of COVID-19 Pneumonia.

The coronavirus disease 2019 (COVID-19) pneumonia is a recent outbreak in mainland China and has rapidly spread to multiple countries worldwide. Pulmonary parenchymal opacities are often observed during chest radiography. Currently, few cases have reported the complications of severe COVID-19 pneumonia. We report a case where serial follow-up chest computed tomography revealed progression of pulmonary lesions into confluent bilateral consolidation with lower lung predominance, thereby confirming COVID-19 pneumonia. Furthermore, complications such as mediastinal emphysema, giant bulla, and pneumothorax were also observed during the course of the disease.

[Development of a giant bulla under spontaneous breathing by self-inflicted lung injury in a patient with COVID-19 pneumonia]. / Entwicklung einer Riesenbulla unter Spontanatmung durch "patient self-inflicted lung injury" bei COVID-19-Pneumonie.

The outbreak of SARS-CoV­2 and the associated COVID-19 pandemic pose major challenges to healthcare systems worldwide. New data on diagnosis, clinical presentation and treatment of the disease are published on a daily basis. This case report describes the fatal course of severe COVID-19 pneumonia in an 81-year-old patient with no previous pulmonary disease who developed a giant bulla during non-invasive high-flow oxygen therapy. Virus-induced diffuse destruction of alveolar tissue or patient self-inflicted lung injury (P-SILI) are discussed as possible pathomechanisms. Future studies must determine whether lung-protective mechanical ventilation with high levels of sedation and paralysis to suppress spontaneous respiratory drive and to reduce transpulmonary pressure can prevent structural lung damage induced both by the virus and P­SILI in COVID-19 patients with ARDS.

Autoimmune mucocutaneous blistering diseases after SARS-Cov-2 vaccination: A Case report of Pemphigus Vulgaris and a literature review.

BACKGROUND: Cases of severe autoimmune blistering diseases (AIBDs) have recently been reported in association with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. AIMS: To describe a report of oropharyngeal Pemphigus Vulgaris (OPV) triggered by the mRNABNT162b2 vaccine (Comirnaty®/ Pfizer/ BioNTech) and to analyze the clinical and immunological characteristics of the AIBDs cases reported following the SARS-CoV-2 vaccination. METHODS: The clinical and immunological features of our case of OPV were documented. A review of the literature was conducted and only cases of AIBDs arising after the SARS-CoV-2 vaccination were included. CASE REPORT: A 60-year old female patients developed oropharyngeal and nasal bullous lesions seven days after the administration of a second dose of the mRNABNT162b2 vaccine (Comirnaty®/ Pfizer/BioNtech). According to the histology and direct immunofluorescence findings showing the presence of supra-basal blister and intercellular staining of IgG antibodies and the presence of a high level of anti-Dsg-3 antibodies (80 U/ml; normal < 7 U/ml) in the serum of the patients, a diagnosis of oropharyngeal Pemphigus Vulgaris was made. REVIEW: A total of 35 AIBDs cases triggered by the SARS-CoV-2 vaccination were found (including our report). 26 (74.3%) were diagnosed as Bullous Pemphigoid, 2 (5.7%) as Linear IgA Bullous Dermatosis, 6 (17.1%) as Pemphigus Vulgaris and 1 (2.9%) as Pemphigus Foliaceus. The mean age of the sample was 72.8 years and there was a predominance of males over females (F:M=1:1.7). In 22 (62.9%) cases, the disease developed after Pfizer vaccine administration, 6 (17.1%) after Moderna, 3 (8.6%) after AstraZeneca, 3 (8.6%) after CoronaVac (one was not specified). All patients were treated with topical and/or systemic corticosteroids, with or without the addition of immunosuppressive drugs, with a good clinical response in every case. CONCLUSION: Clinicians should be aware of the potential, though rare, occurrence of AIBDs as a possible adverse event after the SARS-CoV-2 vaccination. However, notwithstanding, they should encourage their patients to obtain the vaccination in order to assist the public health systems to overcome the COVID-19 pandemic.

Pneumothorax with Bullous Lesions as a Late Complication of Covid-19 Pneumonia: A Report on Two Clinical Cases.

BACKGROUND: Coronavirus-19 disease (COVID-19) primarily affects the respiratory tract, causing viral pneumonia with fever, hypoxemia, and cough. Commonly observed complications include acute respiratory failure, liver or kidney injury, and cardiovascular or neurologic symptoms. In some patients, inflammatory damage results in long-term complications, such as pulmonary fibrosis, chronic pulmonary thrombotic microangiopathy, or neurologic symptoms. The development of spontaneous pneumothorax is reported as a rare complication mainly in consequence to mechanic ventilation in the criticall ill. CASE REPORT: We report 2 cases of patients with COVID-19 pneumonia complicated by spontaneous pneumothorax and bullous lesions of the lung. Bilateral giant bullae were observed in 1 of the cases. This complication occurred after an initial resolvement of respiratory symptoms (day 16 and day 29 after COVID-19 treatment was started). Initially, both patients had shown a rather mild course of COVID-19 pneumonia and no mechanical ventilatory support had been necessary. Why Should an Emergency Physician Be Aware of This?: In both cases, COVID-19 caused alveolar damage and the formation of thoracic bullae with consequent spontaneous pneumothorax as a serious complication. Emergency physicans must be aware of this complication even if the initial COVID-19 symptoms have resolved. © 2021 Elsevier Inc.

Computed tomography features of COVID-19 in children: A systematic review and meta-analysis.

BACKGROUND: There are few reports on the chest computed tomography (CT) imaging features of children with coronavirus disease 2019 (COVID-19), and most reports involve small sample sizes. OBJECTIVES: To systematically analyze the chest CT imaging features of children with COVID-19 and provide references for clinical practice. DATA SOURCES: We searched PubMed, Web of Science, and Embase; data published by Johns Hopkins University; and Chinese databases CNKI, Wanfang, and Chongqing Weipu. METHODS: Reports on chest CT imaging features of children with COVID-19 from January 1, 2020 to August 10, 2020, were analyzed retrospectively and a meta-analysis carried out using Stata12.0 software. RESULTS: Thirty-seven articles (1747 children) were included in this study. The heterogeneity of meta-analysis results ranged from 0% to 90.5%. The overall rate of abnormal lung CT findings was 63.2% (95% confidence interval [CI]: 55.8%-70.6%), with a rate of 61.0% (95% CI: 50.8%-71.2%) in China and 67.8% (95% CI: 57.1%-78.4%) in the rest of the world in the subgroup analysis. The incidence of ground-glass opacities was 39.5% (95% CI: 30.7%-48.3%), multiple lung lobe lesions was 65.1% (95% CI: 55.1%-67.9%), and bilateral lung lesions was 61.5% (95% CI: 58.8%-72.2%). Other imaging features included nodules (25.7%), patchy shadows (36.8%), halo sign (24.8%), consolidation (24.1%), air bronchogram signs (11.2%), cord-like shadows (9.7%), crazy-paving pattern (6.1%), and pleural effusion (9.1%). Two articles reported 3 cases of white lung, another reported 2 cases of pneumothorax, and another 1 case of bullae. CONCLUSIONS: The lung CT results of children with COVID-19 are usually normal or slightly atypical. The lung lesions of COVID-19 pediatric patients mostly involve both lungs or multiple lobes, and the common manifestations are patchy shadows, ground-glass opacities, consolidation, partial air bronchogram signs, nodules, and halo signs; white lung, pleural effusion, and paving stone signs are rare. Therefore, chest CT has limited value as a screening tool for children with COVID-19 and can only be used as an auxiliary assessment tool.