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014 Differential gene expression in lesional skin may signify immune-mediated lung parenchymal damage in dermatomyositis patients [Meeting Abstract]
Shaw, K; Doudican, N; Frazzette, N; Caplan, A; Femia, A; Carucci, J
Dermatomyositis (DM) is an autoimmune connective tissue disease that most commonly affects skin and muscles. Clinical manifestations can be protean, with some patients experiencing skin-limited disease while others develop serious systemic complications including interstitial lung disease (ILD). While both T cell-mediated and humoral immune dysregulation have been purported to play a role in manifesting said end-organ damage, our understanding of immunophenotypic prognostic factors associated with the development of ILD in DM patients remains limited. Thus, we sought to identify potential biomarkers that might be differentially expressed in lesional skin obtained from DM patients with versus without ILD. Utilizing NanoString technology, we assessed differential mRNA expression of 800 immune-related genes in formalin-fixed, paraffin-embedded lesional skin samples obtained from five DM patients with ILD compared to five DM patients without ILD. Among 42 highly regulated genes, 10 were significantly (p<0.05) upregulated in DM patients with ILD: CD44, NFKBIZ, CD24, EGR1, DEFB103B, CCL18, CCL22, CXCL2, S100A8 and S100A9. Notably, serum levels of S100A8/A9 heterodimer (an endogenous ligand of Toll-like receptor 4) are known to correlate with clinical severity in patients with DM-associated ILD, thereby supporting NanoString's utility in identifying salient genes associated with end-organ damage in DM. We also identified several novel genes downregulated in patients with DM-associated ILD that play a role in autophagy and adaptive immune activation: CLEC7, LEF1, KLRC2, BTLA, MUC1, and TCF7. Taken together, our results begin to characterize an immune-related gene expression signature in lesional DM skin that may be associated with comorbid ILD. While validation experiments are ongoing, the identification of biomarkers of systemic disease in lesional DM skin not only has the potential for risk stratifying DM patients at the time of tissue diagnosis but may provide novel targets for early intervention against DM-associated ILD.
Copyright
EMBASE:2019236586
ISSN: 1523-1747
CID: 5291982
Urticarial dermatitis herpetiformis: A rare presentation of an uncommon disorder [Case Report]
Sally, Rachel; Kim, Randie; Lo Sicco, Kristen; Caplan, Avrom S
PMCID:9294481
PMID: 35865727
ISSN: 2352-5126
CID: 5279382
The Evolving Landscape of Cutaneous Sarcoidosis: Pathogenic Insight, Clinical Challenges, and New Frontiers in Therapy
Wu, Julie H; Imadojemu, Sotonye; Caplan, Avrom S
Sarcoidosis is a multisystem disorder of unknown etiology characterized by accumulation of granulomas in affected tissue. Cutaneous manifestations are among the most common extrapulmonary manifestations in sarcoidosis and can lead to disfiguring disease requiring chronic therapy. In many patients, skin disease may be the first recognized manifestation of sarcoidosis, necessitating a thorough evaluation for systemic involvement. Although the precise etiology of sarcoidosis and the pathogenic mechanisms leading to granuloma formation, persistence, or resolution remain unclear, recent research has led to significant advances in our understanding of this disease. This article reviews recent advances in epidemiology, sarcoidosis clinical assessment with a focus on the dermatologist's role, disease pathogenesis, and new therapies in use and under investigation for cutaneous and systemic sarcoidosis.
PMID: 35583850
ISSN: 1179-1888
CID: 5284292
Reactive granulomatous dermatitis: A useful and encompassing term
Wanat, Karolyn Ann; Caplan, Avrom; Messenger, Elizabeth; English, Joseph C; Rosenbach, Misha
PMCID:9006642
PMID: 35434665
ISSN: 2666-3287
CID: 5218142
Terbinafine induced pancreatitis in a healthy young adult male [Letter]
Brydges, Hilliard T; Onuh, Ogechukwu C; Nasr, Hani Y; Gonda, Tamas A; Chiu, Ernest S; Caplan, Avrom S
PMID: 35620915
ISSN: 1529-8019
CID: 5248072
A Woman With Painful Digital Ulcers
Karagounis, Theodora; Belmont, H Michael; Caplan, Avrom S
PMID: 35344026
ISSN: 1538-3598
CID: 5200912
Clinical and Histopathological Spectrum of Delayed Adverse Cutaneous Reactions Following COVID-19 Vaccination
Larson, Valerie; Seidenberg, Roy; Caplan, Avrom; Brinster, Nooshin K; Meehan, Shane A; Kim, Randie H
BACKGROUND:As more people become vaccinated against the SARS-CoV-2 virus, reports of delayed cutaneous hypersensitivity reactions are beginning to emerge. METHODS:In this IRB-approved retrospective case series, biopsies of potential cutaneous adverse reactions from the Pfizer-BioNTech or Moderna mRNA vaccine were identified and reviewed. Clinical information was obtained through the requisition form, referring clinician, or medical chart review. RESULTS:Twelve cases were included. Histopathological features from two injection site reactions showed a mixed-cell infiltrate with eosinophils and a spongiotic dermatitis with eosinophils. Three biopsies came from generalized eruptions that demonstrated interface changes consistent with an exanthematous drug reaction. Three biopsies revealed a predominantly spongiotic pattern, consistent with eczematous dermatitis. Small vessel vascular injury was seen in two specimens, which were diagnosed as urticarial vasculitis and leukocytoclastic vasculitis, respectively. There were two cases of new-onset bullous pemphigoid supported by histopathological examination and direct immunofluorescence studies. Eosinophils were seen in 10 cases. CONCLUSIONS:Dermatopathologists should be aware of potential cutaneous adverse reactions to mRNA-based COVID-19 vaccines. Histopathological patterns include mixed-cell infiltrates, epidermal spongiosis, and interface changes. Eosinophils are a common finding but are not always present. Direct immunofluorescence studies may be helpful for immune-mediated cutaneous presentations such as vasculitis or bullous pemphigoid. This article is protected by copyright. All rights reserved.
PMID: 34292611
ISSN: 1600-0560
CID: 4948502
Corticosteroid use in chronic dermatologic disorders and osteoporosis
Lupsa, Beatrice C; Insogna, Karl L; Micheletti, Robert G; Caplan, Avrom
Glucocorticoid-induced osteoporosis (GIOP) is a frequently encountered and serious side effect of glucocorticoid use. Bone loss leading to an increased risk for fracture occurs early in the use of glucocorticoids, yet patients at risk for this complication are often undertreated. All physicians prescribing glucocorticoids should therefore be familiar with a basic approach to anticipating and preventing GIOP when starting patients on glucocorticoid therapy. This manuscript and its case vignettes are designed to help dermatologists assess and manage bone health to prevent GIOP in patients receiving glucocorticoid therapy.
PMCID:8721058
PMID: 35024411
ISSN: 2352-6475
CID: 5116302
Chronic hydroxychloroquine therapy and COVID-19 outcomes: A retrospective case-control analysis
Rangel, Lauren K; Shah, Payal; Lo Sicco, Kristen; Caplan, Avrom S; Femia, Alisa
PMCID:7797175
PMID: 33440213
ISSN: 1097-6787
CID: 4835312
Advances in cutaneous vasculitis research and clinical care
Caplan, Avrom; Micheletti, Robert G
Vasculitis is characterized by inflammation and destruction of blood vessels, resulting in downstream ischemic tissue damage. Diagnosis of vasculitis is a careful exercise in clinical-pathologic correlation, depending upon the clinical manifestations, organs involved, the size of affected blood vessels, imaging, and laboratory findings. While some vasculitis subtypes may be confined to the skin, serious internal organ involvement or underlying disease states may also occur. Accordingly, the skin plays an important role in the diagnostic process and may be prognostically important in some cases, signifying more severe systemic disease. The skin also provides opportunities for tissue-based translational research, improving understanding of disease pathophysiology. Dermatologists, therefore, play a critical role in evaluating vasculitis and helping to advance vasculitis clinical care and research. Recent updates in vasculitis nomenclature and terminology, evidence-based diagnosis, pathogenesis, and investigations of targeted therapies are changing vasculitis research and leading to fundamental shifts in disease management. Treatment advances favoring evidence-based and targeted, rather than broadly immunosuppressive, therapies are in development, while a multicenter trial for skin-limited vasculitis is ongoing. Collaborative multidisciplinary research networks are key to current and future advances in vasculitis research. In this review, we describe recent developments in vasculitis clinical care and research, starting with a discussion of efforts to develop diagnostic and classification criteria, followed by updates on the evaluation and treatment of vasculitis.
PMCID:8033321
PMID: 33842660
ISSN: 2305-5839
CID: 4953882