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Background/Aims Advances in rational drug design and recent clinical trials are leading to emergence of a range of novel therapies for SLE and therapeutic options in clinical practice are expected to broaden rapidly. The optimal real-world place of emerging and established agents will be guided by understanding their differential efficacy on specific SLE manifestations as well as efficacy for more resistant disease. Anifrolumab, a type-I interferon receptor blocking monoclonal antibody, showed efficacy in SLE in phase III trials with a notable effect on mucocutaneous disease although specific lesion subtypes and chroncicity were not explored. Severe refractory mucocutaneous SLE such as scarring discoid lesions are an important and common clinical challenge in current practice. We therefore prospectively evaluated the real-world efficacy and quality of life impact of anifolumab for active mucocutaneous SLE, recalcitrant to multiple biologic and immunosuppressant therapies. Methods Seven patients commenced anifrolumab (300mg by monthly iv infusion) following application to the manufacturer's early access programme (NCT 04750057). Prior biologic therapies were discontinued at least 5 half-lives in advance. Mucocutaneous disease activity was captured by Cutaneous Lupus Disease Area and Severity Index (CLASI) activity score and medical photography. Patient reported health-related quality of life comprising the Dermatology Life Quality Index (DLQI);Lupus-QoL and EQ5D-5L were evaluated at baseline, three and six months. Results Seven female patients with active mucocutaneous SLE (Discoid LE n=5, chilblain LE n=1, subacute cutaneous LE n=1) and median disease duration of 17 years were evaluated. Median baseline CLASI activity score was 17 (range 10-26;higher scores indicating severe disease). Median number of previously failed therapies was 7 and included rituximab in 6/7, belimumab in 2/7 and thalidomide in 4/7. Rapid resolution of scale and erythema in DLE was established within 1 month of anifrolumab treatment. Improvements to chilblain lupus were evident by three months. CLASI activity score was improved >=75% in all patients at 3 months. Clinical responses were associated with significant improvements in DLQI (p<0.001) and EQ5D-VAS (p=0.002) by three months. Lupus-QoL trended toward improvement across all domains but most strongly for fatigue (p=0.01) and pain (p=0.002) by 6 months. One patient discontinued treatment after 4 months due to polydermatomal shingles complicated by sensorineural hearing loss. Infection coincided with background prednisolone dose >15mg daily, recent COVID-19 infection and new on-treatment hypogammaglobulinaemia (IgG <5g/L). Prolonged aciclovir treatment was required for lesion resolution. Conclusion We report rapid real-world efficacy and quality of life impact of anifrolumab on highly refractory mucocutaneous SLE, which exceeded that anticipated from existing clinical trial data. Findings suggest a unique role for emerging interferon targeting therapies in management of mucocutaneous SLE but emphasize need for enhanced VZV precautions among higher risk patients.
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Hydroxychloroquine (HCQ) is a multi-functional drug owing to its lysosomotropic, immunomodulatory, anti-inflammatory, anti-infective, antithrombotic, antitumoral (pronounced effects on autophagy and apoptosis processes) and beneficial metabolic properties (improved lipid profiles, decreased insulin resistance). We know that chronic low-dose HCQ therapy has been successfully used in a variety of chronic diseases such as rheumatological and dermatological disorders. Additionally, with all these effects mentioned above and showing synergism, HCQ can also be useful mostly as an adjuvant in the management of many chronic metabolic disorders, serious life-threatening conditions such as cardiovascular, neurological, oncological and infectious diseases, as well as their accompanying morbidities. More recently, this former drug, whose effectiveness has been shown in the global coronavirus disease 2019 (COVID-19) pandemic, has entered the spotlight again. Ongoing clinical trials testing HCQ in new indications and challenging diseases are still receiving great attention. In this article, the mechanisms of action, current clinical uses and new indications of HCQ therapy have been overviewed with a comprehensive literature review.Copyright © Necati Ozpinar. All rights reserved.
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Numerous cutaneous reactions have been reported secondary to COVID-19 vaccinations. The most commonly reported include local site reactions, delayed large local reactions, urticaria and morbilliform eruptions. Here we report a case of de novo subacute cutaneous lupus erythematosus (SCLE) after COVID-19 immunization. A 56-year-old woman presented with a 3-month history of a rash. The onset was 1 week following the first dose of the AstraZeneca COVID-19 vaccine. She reported lesions characterized by erythema, pruritus and a burning sensation. She also described mouth dryness. Examination revealed scaly annular erythematous plaques on the chest, arms, legs and scalp. Blood results were positive for anti-Ro antibodies and strongly positive for anti-nuclear antibodies (1: 2560 titre). Anti-Smith, anti-centromere and double- stranded DNA antibodies were negative. Skin biopsy revealed the histological appearance of an interface of dermatitis. Direct immunofluorescence was negative. These clinical and histopathological findings are consistent with a diagnosis of SCLE. The patient was treated with hydroxychloroquine, a weaning course of prednisolone, topical steroids and topical tacrolimus. Her hydroxychloroquine dose was 200 mg twice daily for the first 3 months and then increased to 400 mg twice daily. This resulted in an improvement of her presentation although she has yet to achieve complete remission. It has been suggested that enhanced interferon responses with COVID-19 vaccination and interactions of the SARS-CoV-2 spike protein with cytoplasmic RNA-binding proteins could contribute to disease flares in lupus. There are two other recent reports of SCLE developing or being exacerbated by COVID-19 vaccination. More research is required to determine how COVID-19 vaccinations affect patients with autoimmune skin diseases.
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[Formula presented] Kikuchi-Fujimoto: A Case Report Hickman, JD. MD LT MC USN and An, Joseph, DO. LCDR MC USN Naval Medical Center Portsmouth 620 Johns Paul John Cir, Portsmouth VA 757-953-2223 The views expressed in this are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States Government. We are military service members and employees of the U.S. Government. This work was prepared as part of my official duties. Title 17 U.S.C. 105 provides that “Copyright protection under this title is not available for any work of the United States Government.” Title 17 U.S.C. 101 defines a United States Government work as a work prepared by a military service member or employee of the United States Government as part of that person's official duties. Kikuchi-Fujimoto disease is a rare benign disorder often presenting with tender cervical lymphadenopathy, fever, and malaise. While first described in Japan, its distribution is worldwide and predominantly seen in young adults. Diagnosis is based on characteristic histopathologic findings of patchy necrosis occupied by karyorrhectic debris and abundant histiocytes on node biopsy. The origin is unclear but associated with a preceding viral illness as well as cutaneous lupus erythematosus. Treatment is generally supportive and focused on managing tender lymph nodes. We present a case of a 28-year-old female presenting with a 2 month history of night sweats, fever, and weight loss in the setting of painful neck swelling. CT and PET/CT imaging demonstrated numerous hypermetabolic and enlarged nodes in the bilateral cervical and axillary regions. Lab studies were notable for leukopenia, anemia, and elevated inflammatory markers. A COVID-19 screening was negative. Excisional biopsy of a cervical node revealed extensive cortical necrosis and apoptotic debris with scattered histiocytes and plasmacytoid dendritic cells in absence of neutrophils or a monoclonal B cell or T cell population. Treatment was initiated with NSAIDs and close monitoring. The patient exhibited a complete response after two months. Our case is an important reminder that lymphadenopathy, fever, and night sweats in a young adult are not pathognomonic for lymphoma. Nonetheless, a high suspicion for lymphoma should be maintained and followed with an expedited workup. Kikuchi-Fujimoto can certainly mimic Hodgkin lymphoma or other serious conditions like lupus erythematosus and tuberculosis. The diagnosis is largely one of exclusion following a careful examination of a lymph node histopathology and must be considered in young previously healthy adults to avoid misdiagnosis and unnecessary escalation of treatment. Disclosures: No relevant conflicts of interest to declare.