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Miyazaki S, Goto M, Nakata K, Omura Y, Nishida H, Hatano Y. A case of lupus erythematosus profundus with granulomatous changes with remission achieved by hydroxychloroquine. J Dermatol 2025; 52:e292-e293. [PMID: 39606928 DOI: 10.1111/1346-8138.17561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 10/19/2024] [Accepted: 11/16/2024] [Indexed: 11/29/2024]
Affiliation(s)
- Sayuri Miyazaki
- Department of Dermatology, Faculty of Medicine, Oita University, Oita, Japan
| | - Mizuki Goto
- Department of Dermatology, Faculty of Medicine, Oita University, Oita, Japan
| | - Kyoko Nakata
- Department of Dermatology, Faculty of Medicine, Oita University, Oita, Japan
| | - Yuichi Omura
- Department of Rheumatology, Faculty of Medicine, Oita University, Oita, Japan
| | - Haruto Nishida
- Department of Diagnostic Pathology, Faculty of Medicine, Oita University, Oita, Japan
| | - Yutaka Hatano
- Department of Dermatology, Faculty of Medicine, Oita University, Oita, Japan
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Joseph JM, Kilgore J, Culotta N. Refractory Dermatitis Evolving Into Lupus Spectrum Disease in the Setting of Dupilumab Use. Cureus 2025; 17:e79567. [PMID: 40151702 PMCID: PMC11947495 DOI: 10.7759/cureus.79567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/24/2025] [Indexed: 03/29/2025] Open
Abstract
Cutaneous lupus erythematosus (CLE) encompasses a broad range of clinical and histopathologic variants that can overlap with other dermatologic entities, complicating accurate diagnosis. We report the case of a 42-year-old male patient who initially presented with a diffuse pruritic eruption presumed to be atopic dermatitis, for which dupilumab was initiated. Within the following weeks, the patient developed a fever of unknown origin and diarrhea, raising concern for an atypical drug-related reaction or an unmasked autoimmune process. Subsequent biopsies demonstrated evolving histopathologic features, including superficial and deep perivascular dermatitis suggestive of drug eruption. In addition, a dermal mucin deposition with mixed neutrophilic and lymphocytic infiltrates is suggestive of cutaneous lupus, such as tumid lupus or lupus-related neutrophilic urticarial dermatosis. Despite negative direct immunofluorescence and fluctuating autoantibodies, partial and sustained clinical improvement occurred with hydroxychloroquine therapy. The patient's variable serologic profile (including intermittent positivity for antiribonucleoprotein and anti-Smith), transient urticarial lesions, and evolving histopathology highlight the difficulties in definitively categorizing cutaneous lupus subtypes. While a direct causal link between dupilumab and lupus-like disease remains unproven, the temporal association raises the possibility that T helper type 1/T helper type 2 immune modulation may unmask subclinical autoimmune conditions. This case underscores the importance of repeated clinicopathologic correlation and multidisciplinary surveillance in patients presenting with atypical or treatment-refractory dermatitis. Ongoing dermatologic and rheumatologic evaluation is critical for early detection of systemic involvement, especially when autoimmune etiologies are suspected. Hydroxychloroquine remains a cornerstone of therapy for many CLE variants and can provide substantial improvement, even in complex or overlapping clinical scenarios.
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Affiliation(s)
- Jonathan M Joseph
- Department of Dermatology, Louisiana State University (LSU) Health, New Orleans, USA
| | - Jacob Kilgore
- Department of Dermatology, Louisiana State University (LSU) Health, New Orleans, USA
| | - Nicholas Culotta
- Department of Dermatology, Louisiana State University (LSU) Health, New Orleans, USA
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Joveini S, Yarmohammadi F, Iranshahi M, Nikpoor AR, Askari VR, Attaranzadeh A, Etemad L, Taherzadeh Z. Distinct therapeutic effects of auraptene and umbelliprenin on TNF-α and IL-17 levels in a murine model of chronic inflammation. Heliyon 2024; 10:e40731. [PMID: 39687160 PMCID: PMC11648749 DOI: 10.1016/j.heliyon.2024.e40731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Revised: 11/23/2024] [Accepted: 11/25/2024] [Indexed: 12/18/2024] Open
Abstract
Objective To compare the anti-arthritic potential of orally administered auraptene (AUR) and umbellliprenin (UMB) in chronic inflammation by exploring the differential effect on regulating TNF-α and IL-17. Methods & materials Sixty male rats were divided into ten groups, and after confirming chronic inflammation, the treatment groups received AUR or UMB orally for 9 days. On day 16, histopathological changes were evaluated. Altered serum levels of the inflammatory cytokines TNF-α and IL-17 were examined as the underlying mechanisms. Results Administering AUR orally at 16 mM/kg caused a significant increase in body weight gain compared to the baseline (p < 0.05), while UMB at a dose of 64 mM/kg significantly reduced edema size (p < 0.01). TNF-α levels were significantly lower in all doses of AUR and UMB treatments compared to the arthritis control group (p < 0.05). Treatment with AUR at all relative doses resulted in a significant decrease in IL-17 levels compared to the arthritis control group (p < 0.05), whereas UMB treatment did not show a significant effect on IL-17 levels. Conclusion AUR and UMB regulate TNF-α and IL-17 differently; AUR inhibits both, showing broad therapeutic potential, while UMB specifically targets TNF-α, showing a specialized role.
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Affiliation(s)
- Saeid Joveini
- Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fatemeh Yarmohammadi
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mehrdad Iranshahi
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amin Reza Nikpoor
- Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
| | - Vahid Reza Askari
- Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Armin Attaranzadeh
- Department of Medical Genetics, Faculty of Medicines, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Leila Etemad
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zhila Taherzadeh
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Targeted Drug Delivery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Youvalakshmi S, Logamoorthy R, Karthikeyan K. Drug reaction with eosinophilia and systemic symptoms with toxic epidermal necrolysis like rash in systemic sclerosis and overlapping sjogren's syndrome: A double trouble triggered by a herbal medicine. Indian J Dermatol Venereol Leprol 2024; 0:1-3. [PMID: 39912181 DOI: 10.25259/ijdvl_726_2024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Accepted: 09/15/2024] [Indexed: 02/07/2025]
Affiliation(s)
- Saravanan Youvalakshmi
- Department of Dermatology Venereology and Leprosy, Sri Manakula Vinayagar Medical College & Hospital, Madagadipet, Kalitheerthalkuppam, Pondicherry, India
| | - Ramamoorthy Logamoorthy
- Department of Dermatology Venereology and Leprosy, Sri Manakula Vinayagar Medical College & Hospital, Madagadipet, Kalitheerthalkuppam, Pondicherry, India
| | - Kaliaperumal Karthikeyan
- Department of Dermatology Venereology and Leprosy, Sri Manakula Vinayagar Medical College & Hospital, Madagadipet, Kalitheerthalkuppam, Pondicherry, India
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Natalucci F, Ceccarelli F, Picciariello L, Olivieri G, Ciancarella C, Alessandri C, Conti F. Are Tattoos Safe in Patients with Systemic Lupus Erythematosus? Results From a Single-Center Study. Dermatol Pract Concept 2024; 14:dpc.1404a230. [PMID: 39652953 PMCID: PMC11619997 DOI: 10.5826/dpc.1404a230] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/19/2024] [Indexed: 12/12/2024] Open
Abstract
INTRODUCTION Systemic Lupus Erythematosus is a pleiotropic autoimmune disease with common skin involvement. To date, only one study has investigated tattoos safety in SLE patients. OBJECTIVE We performed a single-center study to evaluate the development of local and systemic complications after tattooing in a cohort of systemic lupus erythematosus (SLE) patients. Furthermore, we tried to identify SLE patients who had expressed the will to get a tattoo and why they decided not to. METHODS Consecutive SLE patients were asked to complete a questionnaire about tattoos, including their number, features, and side effects. Open questions were proposed to non-tattooed patients to describe why they did not have tattoos. RESULTS One hundred ninety-two SLE patients were enrolled [M/F 21/171; median age 41 years (IQR 18)]. Almost 50% of them had at least one tattoo. Seven patients (7.4%) referred adverse reactions to tattoos; interestingly, only one patient experienced a systemic reaction, specifically the occurrence of self-limiting lymphadenopathy. The main reason for not getting a tattoo was the diagnosis of SLE. CONCLUSIONS Our results suggest the safety of tattoos in SLE patients, as demonstrated by a low prevalence of mild adverse events.
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Affiliation(s)
- Francesco Natalucci
- Lupus Clinic, Rheumatology, Dipartimento di Scienze Cliniche Internistiche Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, Roma, Italy
| | - Fulvia Ceccarelli
- Lupus Clinic, Rheumatology, Dipartimento di Scienze Cliniche Internistiche Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, Roma, Italy
| | - Licia Picciariello
- Lupus Clinic, Rheumatology, Dipartimento di Scienze Cliniche Internistiche Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, Roma, Italy
| | - Giulio Olivieri
- Lupus Clinic, Rheumatology, Dipartimento di Scienze Cliniche Internistiche Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, Roma, Italy
| | - Claudia Ciancarella
- Lupus Clinic, Rheumatology, Dipartimento di Scienze Cliniche Internistiche Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, Roma, Italy
| | - Cristiano Alessandri
- Lupus Clinic, Rheumatology, Dipartimento di Scienze Cliniche Internistiche Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, Roma, Italy
| | - Fabrizio Conti
- Lupus Clinic, Rheumatology, Dipartimento di Scienze Cliniche Internistiche Anestesiologiche e Cardiovascolari, Sapienza Università di Roma, Roma, Italy
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Chu C, Soh L, Tan SH, Lee TS, Loh I. Lupus Erythematous Profundus: An Unusual Manifestation in the Otolaryngological Setting. Cureus 2023; 15:e46402. [PMID: 37927642 PMCID: PMC10620982 DOI: 10.7759/cureus.46402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/02/2023] [Indexed: 11/07/2023] Open
Abstract
Lupus erythematous profoundus (LEP) is an uncommon manifestation of chronic lupus erythematous (CLE) involving inflammation of the subcutaneous fat and deep dermis. It is rarely seen in the otolaryngological practice. We describe a case of a 33-year-old female who presented with bilateral acute onset cheek swelling, which led to the unexpected diagnosis of LEP. We describe the diagnostic pitfalls that may potentially bias the surgeon towards the management of such patients.
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Affiliation(s)
- Clarisse Chu
- Otolaryngology, Changi General Hospital, Singapore, SGP
| | - Leonard Soh
- Otolaryngology, Changi General Hospital, Singapore, SGP
| | - Sze Hwa Tan
- Pathology, Changi General Hospital, Singapore, SGP
| | - Tee Sin Lee
- Otolaryngology, Changi General Hospital, Singapore, SGP
| | - Ian Loh
- Otolaryngology, Changi General Hospital, Singapore, SGP
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Liu L, Lian N, Shi L, Hao Z, Chen K. Ferroptosis: Mechanism and connections with cutaneous diseases. Front Cell Dev Biol 2023; 10:1079548. [PMID: 36684424 PMCID: PMC9846271 DOI: 10.3389/fcell.2022.1079548] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 12/16/2022] [Indexed: 01/05/2023] Open
Abstract
Ferroptosis is a recognized novel form of programmed cell death pathway, featuring abnormalities in iron metabolism, SystemXc-/glutathione axis, and lipid peroxidation regulation. A variety of ferroptosis inducers can influence glutathione peroxidase directly or indirectly via diverse pathways, leading to decreased antioxidant capacity, accumulated cellular lipid peroxides, and finally inducing ferroptosis. To date, mounting studies confirm the association of ferroptosis with various cutaneous diseases, including skin homeostasis, neoplastic diseases, infectious diseases, genetic skin disease, inflammatory skin diseases, and autoimmune diseases. There are shared characteristics regarding ferroptosis and various cutaneous diseases in terms of pathophysiological mechanisms, such as oxidative stress associated with iron metabolism disorder and accumulated lipid peroxides. Therefore, we summarize the current knowledge regarding the mechanisms involved in the regulation of ferroptosis for further discussion of its role in the pathogenesis and prognosis of skin diseases. Gaining insight into the underlying mechanisms of ferroptosis and the associated dermatological disorders could illuminate the pathogenesis and treatments of different cutaneous diseases.
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Affiliation(s)
- Lihao Liu
- Department of Physiotherapy, Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Nanjing, China
| | - Ni Lian
- Department of Dermatology, Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Nanjing, Jiangsu, China
| | - Liqing Shi
- Department of Dermatology, Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Nanjing, Jiangsu, China
| | - Zhimin Hao
- Department of Dermatology, Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Nanjing, Jiangsu, China
| | - Kun Chen
- Department of Physiotherapy, Institute of Dermatology, Chinese Academy of Medical Sciences, Peking Union Medical College, Nanjing, China,*Correspondence: Kun Chen,
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Stull C, Sprow G, Werth VP. Cutaneous Involvement in Systemic Lupus Erythematosus: A Review for the Rheumatologist. J Rheumatol 2023; 50:27-35. [PMID: 36109075 PMCID: PMC10152495 DOI: 10.3899/jrheum.220089] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/25/2022] [Indexed: 02/08/2023]
Abstract
The majority of patients with systemic lupus erythematosus (SLE) have cutaneous manifestations at some point in their disease course. The skin findings in SLE are classified as SLE-specific or SLE-nonspecific based on histopathologic findings. SLE-specific skin diseases include chronic cutaneous lupus erythematosus (CLE), subacute CLE, and acute CLE. There are subsets of skin lesions within each group and the likelihood of associated SLE varies among them. SLE-nonspecific lesions are more common in patients with SLE and tend to coincide with active systemic disease. SLE-nonspecific lesions may be seen as a feature of another disease process, including other connective tissue diseases. It is important for the rheumatologist to be familiar with the spectrum of cutaneous diseases in SLE to help prognosticate the likelihood of systemic disease and to ensure patients receive timely dermatologic care with the goal of controlling disease activity to prevent damage.
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Affiliation(s)
- Courtney Stull
- C. Stull, MD, Corporal Michael J. Crescenz VAMC, and Department of Dermatology, University of Pennsylvania, Philadelphia, and Department of Rheumatology, University of Pittsburgh Medical Center, Pittsburgh
| | - Grant Sprow
- G. Sprow, BA, V.P. Werth, MD, Corporal Michael J. Crescenz VAMC, and Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Victoria P Werth
- G. Sprow, BA, V.P. Werth, MD, Corporal Michael J. Crescenz VAMC, and Department of Dermatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
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Drenkard C, Barbour KE, Greenlund KJ, Lim SS. The Burden of Living With Cutaneous Lupus Erythematosus. Front Med (Lausanne) 2022; 9:897987. [PMID: 36017007 PMCID: PMC9395260 DOI: 10.3389/fmed.2022.897987] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 05/24/2022] [Indexed: 11/13/2022] Open
Abstract
Cutaneous lupus erythematosus (CLE) is a group of heterogeneous autoimmune disorders primarily affecting the skin. Patients with these conditions are mostly young women when they become sick and often suffer from recurrent skin symptoms or longstanding changes in their physical appearance. CLE disorders lead to different levels of morbidity and can impact profoundly patients' quality of life, particularly in the psychological and social health domains. This review provides a summary of recent research investigating the psychosocial burden of living with CLE and the intersect amongst the disease characteristics, patient factors, and social determinants of health. Furthermore, this review provides insight into patient care and research needs that remain unmet to improve the quality of life of patients living with CLE.
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Affiliation(s)
- Cristina Drenkard
- Division of Rheumatology, Department of Medicine, Emory School of Medicine, Atlanta, GA, United States
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United States
- *Correspondence: Cristina Drenkard
| | - Kamil E. Barbour
- Centers for Disease Control and Prevention, Atlanta, GA, United States
| | - Kurt J. Greenlund
- Centers for Disease Control and Prevention, Atlanta, GA, United States
| | - S. Sam Lim
- Division of Rheumatology, Department of Medicine, Emory School of Medicine, Atlanta, GA, United States
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, United States
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Drenkard C, Theis KA, Daugherty TT, Helmick CG, Dunlop-Thomas C, Bao G, Aspey L, Lewis TT, Lim SS. Depression, stigma and social isolation: the psychosocial trifecta of primary chronic cutaneous lupus erythematosus, a cross-sectional and path analysis. Lupus Sci Med 2022; 9:e000697. [PMID: 35953237 PMCID: PMC9379542 DOI: 10.1136/lupus-2022-000697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Accepted: 07/25/2022] [Indexed: 11/24/2022]
Abstract
OBJECTIVE Depression is common in individuals with chronic cutaneous lupus erythematosus (CCLE). However, how CCLE may impact patients' psychological well-being is poorly understood, particularly among disproportionally affected populations. We examined the relationships between depression and psychosocial factors in a cohort of predominantly Black patients with primary CCLE (CCLE without systemic manifestations). METHODS Cross-sectional assessment of individuals with dermatologist-validated diagnosis of primary CCLE. NIH-PROMIS short-forms were used to measure depression, disease-related stigma, social isolation and emotional support. Linear regression analyses (ɑ=0.05) were used to test an a priori conceptual model of the relationship between stigma and depression and the effect of social isolation and emotional support on that association. RESULTS Among 121 participants (87.6% women; 85.1% Black), 37 (30.6%) reported moderate to severe depression. Distributions of examined variables divided equally among those which did (eg, work status, stigma (more), social isolation (more), emotional support (less)) and did not (eg, age, sex, race, marital status) significantly differ by depression. Stigma was significantly associated with depression (b=0.77; 95% CI0.65 to 0.90), whereas social isolation was associated with both stigma (b=0.85; 95% CI 0.72 to 0.97) and depression (b=0.70; 95% CI0.58 to 0.92). After controlling for confounders, stigma remained associated with depression (b=0.44; 95% CI0.23 to 0.66) but lost significance (b=0.12; 95% CI -0.14 to 0.39) when social isolation (b=0.40; 95% CI 0.19 to 0.62) was added to the model. Social isolation explained 72% of the total effect of stigma on depression. Emotional support was inversely associated with depression in the univariate analysis; however, no buffer effect was found when it was added to the multivariate model. CONCLUSION Our findings emphasise the psychosocial challenges faced by individuals living with primary CCLE. The path analysis suggests that stigmatisation and social isolation might lead to depressive symptoms. Early clinical identification of social isolation and public education demystifying CCLE could help reduce depression in patients with CCLE.
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Affiliation(s)
- Cristina Drenkard
- Department of Medicine/Rheumatology, Emory University School of Medicine, Atlanta, Georgia, USA
- Department of Epidemiology, Emory University School of Public Health, Atlanta, Georgia, USA
| | - Kristina A Theis
- Division of Population Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Timothy T Daugherty
- Department of Medicine, Washington University in St Louis, St Louis, Missouri, USA
| | - Charles G Helmick
- Division of Population Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
| | - Charmayne Dunlop-Thomas
- Department of Medicine/Rheumatology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Gaobin Bao
- Department of Medicine/Rheumatology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Laura Aspey
- Department Medicine/Dermatology, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Tené T Lewis
- Department of Epidemiology, Emory University School of Public Health, Atlanta, Georgia, USA
| | - S Sam Lim
- Department of Medicine/Rheumatology, Emory University School of Medicine, Atlanta, Georgia, USA
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Tappel AC, Tiwari N, Saavedra A. Terbinafine-Induced Relapse of Bullous Lupus Erythematosus. J Clin Rheumatol 2021; 27:S607-S609. [PMID: 30601164 DOI: 10.1097/rhu.0000000000000945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Shimamura Y, Ogawa Y, Takizawa H. Chilblain Lupus Erythematosus. JMA J 2021; 4:423-425. [PMID: 34796299 PMCID: PMC8580682 DOI: 10.31662/jmaj.2021-0064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2021] [Accepted: 06/04/2021] [Indexed: 11/30/2022] Open
Affiliation(s)
| | - Yayoi Ogawa
- Hokkaido Renal Pathology Center, Sapporo, Japan
| | - Hideki Takizawa
- Department of Nephrology, Teine Keijinkai Medical Center, Sapporo, Japan
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Worm M, Zidane M, Eisert L, Fischer-Betz R, Foeldvari I, Günther C, Iking-Konert C, Kreuter A, Müller-Ladner U, Nast A, Ochsendorf F, Schneider M, Sticherling M, Tenbrock K, Wenzel J, Kuhn A. S2k guideline: Diagnosis and management of cutaneous lupus erythematosus - Part 1: Classification, diagnosis, prevention, activity scores. J Dtsch Dermatol Ges 2021; 19:1236-1247. [PMID: 34390136 DOI: 10.1111/ddg.14492] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Margitta Worm
- Department of Dermatology, Venereology and Allergology, Division of Allergology and Immunology Charité - Universitätsmedizin Berlin, corporate member of Free University of Berlin, Humboldt University of Berlin, and Berlin Institute of Health
| | - Miriam Zidane
- Department of Dermatology, Venereology and Allergology, Division of Evidence-Based Medicine Charité - Universitätsmedizin Berlin, corporate member of Free University of Berlin, Humboldt University of Berlin, and Berlin Institute of Health
| | - Lisa Eisert
- Department of Dermatology and Venereology, Vivantes Klinikum Neukölln, Berlin
| | - Rebecca Fischer-Betz
- Clinic and Functional Division for Rheumatology, University Hospital Düsseldorf, Düsseldorf
| | - Ivan Foeldvari
- Hamburg Center for Pediatric and Adolescent Rheumatology, Hamburg
| | - Claudia Günther
- Department of Dermatology, University Hospital Carl Gustav Carus Dresden, and Technical University of Dresden, Dresden
| | - Christof Iking-Konert
- III. Medical Clinic and Polyclinic, Section Rheumatology, University Hospital Hambug-Eppendorf, Hamburg
| | - Alexander Kreuter
- Dermatology, Venereology and Allergology, Helios St. Elisabeth Hospital Oberhausen, and University of Witten-Herdecke, Oberhausen
| | - Ulf Müller-Ladner
- Department of Rheumatology and Clinical Immunology, Kerckhoff Hospital GmbH, Bad Nauheim
| | - Alexander Nast
- Department of Dermatology, Venereology and Allergology, Division of Evidence-Based Medicine Charité - Universitätsmedizin Berlin, corporate member of Free University of Berlin, Humboldt University of Berlin, and Berlin Institute of Health
| | - Falk Ochsendorf
- Department of Dermatology, Venereology and Allergology, University Hospital Frankfurt, Frankfurt am Main
| | - Matthias Schneider
- Clinic and Functional Division for Rheumatology, University Hospital Düsseldorf, Düsseldorf
| | | | - Klaus Tenbrock
- Department of Pediatrics and Adolescent Medicine, University Hospital RWTH Aachen, Aachen
| | - Jörg Wenzel
- Dermatological Department, University Hospital Bonn, Bonn
| | - Annegret Kuhn
- Medical Director, Hospital Passau, Passau, University of Münster, Münster, Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Center, Amsterdam, Niederlande
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14
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Worm M, Zidane M, Eisert L, Fischer-Betz R, Foeldvari I, Günther C, Iking-Konert C, Kreuter A, Müller-Ladner U, Nast A, Ochsendorf F, Schneider M, Sticherling M, Tenbrock K, Wenzel J, Kuhn A. S2k‐Leitlinie zur Diagnostik und Therapie des kutanen Lupus erythematodes – Teil 1: Klassifikation, Diagnostik, Prävention und Aktivitätsscores. J Dtsch Dermatol Ges 2021; 19:1236-1248. [PMID: 34390147 DOI: 10.1111/ddg.14492_g] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Margitta Worm
- Klinik für Dermatologie, Venerologie und Allergologie, Abteilung für Allergologie und Immunologie, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, und Berliner Institut für Gesundheitsforschung, Berlin
| | - Miriam Zidane
- Klinik für Dermatologie, Venerologie und Allergologie, Division of Evidence Based Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, und Berliner Institut für Gesundheitsforschung, Berlin
| | - Lisa Eisert
- Klinik für Dermatologie und Venerologie, Vivantes Klinikum Neukölln, Berlin
| | - Rebecca Fischer-Betz
- Poliklinik und Funktionsbereich für Rheumatologie, Universitätsklinikum Düsseldorf, Düsseldorf
| | - Ivan Foeldvari
- Hamburger Zentrum für Kinder- und Jugendrheumatologie, Hamburg
| | - Claudia Günther
- Klinik und Poliklinik für Dermatologie, Universitätsklinikum Carl Gustav Carus Dresden und Technische Universität Dresden, Dresden
| | - Christof Iking-Konert
- III. Medizinische Klinik und Poliklinik, Sektion Rheumatologie, Universitätsklinikum Hambug-Eppendorf, Hamburg
| | - Alexander Kreuter
- Dermatologie, Venerologie und Allergologie, Helios St. Elisabeth Klinik Oberhausen, Oberhausen Universität Witten-Herdecke, Witten-Herdecke
| | - Ulf Müller-Ladner
- Abteilung für Rheumatologie und Klinische Immunologie, Kerckhoff-Klinik GmbH, Bad Nauheim
| | - Alexander Nast
- Klinik für Dermatologie, Venerologie und Allergologie, Division of Evidence Based Medicine, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, und Berliner Institut für Gesundheitsforschung, Berlin
| | - Falk Ochsendorf
- Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Frankfurt, Frankfurt am Main
| | - Matthias Schneider
- Poliklinik und Funktionsbereich für Rheumatologie, Universitätsklinikum Düsseldorf, Düsseldorf
| | | | - Klaus Tenbrock
- Klinik für Kinder- und Jugendmedizin, Uniklinik RWTH Aachen, Aachen
| | - Jörg Wenzel
- Dermatologische Klinik, Universitätsklinikum Bonn, Bonn
| | - Annegret Kuhn
- Ärztliche Direktion, Klinikum Passau, Passau, Universität Münster, Münster, Department of Rheumatology and Clinical Immunology, Amsterdam University Medical Center, Amsterdam, Niederlande
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15
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Kus KJB, LaChance AH, Vleugels RA. Recognition and Management of Cutaneous Connective Tissue Diseases. Med Clin North Am 2021; 105:757-782. [PMID: 34059249 DOI: 10.1016/j.mcna.2021.04.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Connective tissue diseases (CTDs) encompass a broad spectrum of clinical presentations that involve multidisciplinary management. Cutaneous findings are common in CTD and careful examination of these features aids in appropriate diagnosis and subsequent evaluation. Thorough work-up of CTD is crucial to properly identify disease subtypes and systemic involvement. Management plans can be developed based on diagnosis and systemic manifestations of disease. Disease management often requires treatment with pharmacotherapies with potential for toxicities, further underscoring the importance of diagnostic accuracy in this patient population. Evolving research strives to better elucidate the pathogenic mechanisms of CTDs allowing for more targeted treatment modalities.
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MESH Headings
- Adult
- Comorbidity
- Connective Tissue Diseases/complications
- Connective Tissue Diseases/diagnosis
- Connective Tissue Diseases/drug therapy
- Connective Tissue Diseases/pathology
- Dermatomyositis/diagnosis
- Dermatomyositis/etiology
- Dermatomyositis/pathology
- Diagnosis, Differential
- Drug Therapy/methods
- Drug Therapy/statistics & numerical data
- Drug-Related Side Effects and Adverse Reactions
- Early Diagnosis
- Female
- Humans
- Interdisciplinary Communication
- Lupus Erythematosus, Cutaneous/diagnosis
- Lupus Erythematosus, Cutaneous/etiology
- Lupus Erythematosus, Cutaneous/pathology
- Lupus Erythematosus, Discoid/diagnosis
- Lupus Erythematosus, Discoid/etiology
- Lupus Erythematosus, Discoid/pathology
- Lupus Erythematosus, Systemic/diagnosis
- Lupus Erythematosus, Systemic/etiology
- Lupus Erythematosus, Systemic/pathology
- Male
- Patient Care Management/methods
- Scleroderma, Systemic/diagnosis
- Scleroderma, Systemic/etiology
- Scleroderma, Systemic/pathology
- Vasculitis/diagnosis
- Vasculitis/etiology
- Vasculitis/pathology
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Affiliation(s)
- Kylee J B Kus
- Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA; Oakland University William Beaumont School of Medicine, 586 Pioneer Drive, Rochester, MI 48309-4482, USA
| | - Avery H LaChance
- Connective Tissue Disease Clinic, Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA.
| | - Ruth Ann Vleugels
- Autoimmune Skin Disease Program, Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA.
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16
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Bitar C, Menge TD, Chan MP. Cutaneous manifestations of lupus erythematosus: A practical clinicopathologic review for pathologists. Histopathology 2021; 80:233-250. [PMID: 34197657 DOI: 10.1111/his.14440] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Accepted: 06/30/2021] [Indexed: 11/27/2022]
Abstract
Accurate diagnosis of connective tissue diseases is often challenging and relies on careful correlation between clinical and histopathologic features, direct immunofluorescence studies, and laboratory workup. Lupus erythematosus (LE) is a prototype of connective tissue disease with a variety of cutaneous and systemic manifestations. Microscopically, cutaneous LE is classically characterized by an interface dermatitis, although other histopathologic patterns also exist depending on the clinical presentation, location, and chronicity of the skin lesions. In this article, we review the clinical, serologic, histopathologic, and direct immunofluorescence findings in LE-specific and LE-nonspecific skin lesions, with an emphasis on lesser known variants, newly described features, and helpful ancillary studies. This review will guide general pathologists and dermatopathologists in accurately diagnosing and subclassifying cutaneous LE.
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Affiliation(s)
- Carole Bitar
- Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.,Department of Dermatology, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Tyler D Menge
- Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.,Department of Dermatology, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA
| | - May P Chan
- Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.,Department of Dermatology, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA
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17
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Zhou HY, Cao NW, Guo B, Chen WJ, Tao JH, Chu XJ, Meng X, Zhang TX, Li BZ. Systemic lupus erythematosus patients have a distinct structural and functional skin microbiota compared with controls. Lupus 2021; 30:1553-1564. [PMID: 34139926 DOI: 10.1177/09612033211025095] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
OBJECTIVE The skin is the second most affected organ after articular involvement in systemic lupus erythematosus (SLE) patients. Cutaneous involvement occurs in approximately 80% of patients during the course of SLE. Interaction between the host and skin microorganism is a complex process. There are few studies on the diversity of skin microbes in SLE patients. Therefore, this study aims to explore the relationship between skin microorganisms and SLE. METHODS A total of 20 SLE patients, 20 controls with rosacea and 20 healthy controls were selected as study subjects. Both the skin microbiota of rash region and non-rash region for each SLE patient were collected.16S rRNA gene sequencing was used to detected skin microbiota from 80 specimens. α-Diversity and β-diversity of skin microbiota were analyzed based on operational taxonomic units (OTUs) and minimal entropy decomposition (MED). Using Wilcoxon test and Linear Discriminate Analysis Effect Size (LEfSe), skin microbial diversity and composition were analyzed. Functional capabilities of microbiota were estimated through Kyoto Encyclopedia of Genes and Genomes database. RESULTS Compared to rash region of SLE, diversity and richness were increased in healthy controls, and decreased in non-rash region of SLE and rash region of controls with rosacea. Additionally, changes of skin microbial composition were found at different taxonomic levels between four groups. For example, genus Halomonas was increased and genera Pelagibacterium, Novosphingobium, and Curvibacter were decreased in rash region compared to non-rash region of SLE based on OTUs and MED. Based on OTUs, metabolic pathways were also found differences in SLE patients, such as Xenobiotics Biodegradation and Metabolism. CONCLUSION Compositions and diversity of skin microbiota in SLE patients are changed. This pilot study provides some suggestive evidence for further exploration of skin microbiota in SLE patients with cutaneous involvement.
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Affiliation(s)
- Hao-Yue Zhou
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China.,Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, China
| | - Nv-Wei Cao
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China.,Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, China
| | - Biao Guo
- Department of Human Resource, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Wen-Jun Chen
- Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, Hefei, China
| | - Jin-Hui Tao
- Department of Rheumatology & Immunology, Anhui Provincial Hospital, Hefei, China
| | - Xiu-Jie Chu
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China.,Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, China
| | - Xiang Meng
- College & Hospital of Stomatology, Anhui Medical University, Hefei, China
| | - Tian-Xiang Zhang
- Department of Clinical Medicine, Second Clinical Medical College, Anhui Medical University, Hefei, China
| | - Bao-Zhu Li
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China.,Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, China
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18
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Azrielant S, Ellenbogen E, Peled A, Zemser-Werner V, Samuelov L, Sprecher E, Pavlovsky M. Diffuse Facial Hyperpigmentation as a Presenting Sign of Lupus Erythematosus: Three Cases and Review of the Literature. Case Rep Dermatol 2021; 13:263-270. [PMID: 34177516 PMCID: PMC8215949 DOI: 10.1159/000515732] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Accepted: 03/08/2021] [Indexed: 11/19/2022] Open
Abstract
Lupus erythematosus (LE) is an autoimmune disorder commonly affecting the skin; cutaneous lesions may indicate systemic involvement, warranting further evaluation. Photosensitivity, which may result in hyperpigmentation, is a well-known feature of the disease. In contrast, the prevalence of primary hyperpigmentation as a presenting sign of LE is not well established. Here, we compare 3 unique cases of diffuse facial hyperpigmentation as the primary manifestation of LE (cutaneous or systemic) and review previously reported cases. Our data highlight the need for considering LE in the differential diagnosis of facial hyperpigmentation and substantiate the importance of this unique lupus variant in early diagnosis and patient evaluation.
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Affiliation(s)
- Shir Azrielant
- Division of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Eran Ellenbogen
- Division of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Alon Peled
- Division of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | | | - Liat Samuelov
- Division of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Eli Sprecher
- Division of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Mor Pavlovsky
- Division of Dermatology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
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19
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Herzum A, Gasparini G, Cozzani E, Burlando M, Parodi A. Atypical and Rare Forms of Cutaneous Lupus Erythematosus: The Importance of the Diagnosis for the Best Management of Patients. Dermatology 2021; 238:195-204. [PMID: 34082424 DOI: 10.1159/000515766] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Accepted: 03/07/2021] [Indexed: 11/19/2022] Open
Abstract
Lupus erythematosus (LE) is an autoimmune disease with a wide range of clinical and cutaneous manifestations. Along with the well-known typical cutaneous manifestations of LE, some cutaneous manifestations are rarer, but still characteristic, enabling the dermatologist and the general practitioner who know them to suspect cutaneous LE (CLE) and investigate a possible underlying systemic involvement. Indeed, not infrequently a skin manifestation is the first presentation of systemic LE (SLE), and >75% of SLE patients show signs of skin disease during the course of the illness. Especially, SLE involvement occurs in cases of acute CLE, while it is uncommon in subacute CLE and rare in chronic CLE. This review aims to concentrate especially on atypical cutaneous manifestations of LE to enable the clinician to diagnose even the rarest forms of CLE.
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Affiliation(s)
- Astrid Herzum
- Section of Dermatology, Department of Health Sciences, University of Genoa, Genoa, Italy.,Dermatology Unit, Ospedale Policlinico San Martino IRCCS, Genoa, Italy
| | - Giulia Gasparini
- Section of Dermatology, Department of Health Sciences, University of Genoa, Genoa, Italy.,Dermatology Unit, Ospedale Policlinico San Martino IRCCS, Genoa, Italy.,Department of Specialistic Medicine, University of Genoa, Genoa, Italy
| | - Emanuele Cozzani
- Section of Dermatology, Department of Health Sciences, University of Genoa, Genoa, Italy.,Dermatology Unit, Ospedale Policlinico San Martino IRCCS, Genoa, Italy
| | - Martina Burlando
- Section of Dermatology, Department of Health Sciences, University of Genoa, Genoa, Italy.,Dermatology Unit, Ospedale Policlinico San Martino IRCCS, Genoa, Italy
| | - Aurora Parodi
- Section of Dermatology, Department of Health Sciences, University of Genoa, Genoa, Italy.,Dermatology Unit, Ospedale Policlinico San Martino IRCCS, Genoa, Italy
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20
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Sim JH, Ambler WG, Sollohub IF, Howlader MJ, Li TM, Lee HJ, Lu TT. Immune Cell-Stromal Circuitry in Lupus Photosensitivity. THE JOURNAL OF IMMUNOLOGY 2021; 206:302-309. [PMID: 33397744 DOI: 10.4049/jimmunol.2000905] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Accepted: 11/12/2020] [Indexed: 12/11/2022]
Abstract
Photosensitivity is a sensitivity to UV radiation (UVR) commonly found in systemic lupus erythematosus (SLE) patients who have cutaneous disease. Upon even ambient UVR exposure, patients can develop inflammatory skin lesions that can reduce the quality of life. Additionally, UVR-exposed skin lesions can be associated with systemic disease flares marked by rising autoantibody titers and worsening kidney disease. Why SLE patients are photosensitive and how skin sensitivity leads to systemic disease flares are not well understood, and treatment options are limited. In recent years, the importance of immune cell-stromal interactions in tissue function and maintenance is being increasingly recognized. In this review, we discuss SLE as an anatomic circuit and review recent findings in the pathogenesis of photosensitivity with a focus on immune cell-stromal circuitry in tissue health and disease.
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Affiliation(s)
- Ji Hyun Sim
- Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021.,Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065
| | - William G Ambler
- Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021.,Pediatric Rheumatology, Hospital for Special Surgery, New York, NY 10021
| | - Isabel F Sollohub
- Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021
| | - Mir J Howlader
- Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021.,Biochemistry and Structural Biology, Cell Biology, Developmental Biology, and Molecular Biology Graduate Program, Weill Cornell Graduate School of Medical Sciences, New York, NY 10065; and
| | - Thomas M Li
- Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021
| | - Henry J Lee
- Department of Dermatology, Weill Cornell Medical College, New York, NY 10065
| | - Theresa T Lu
- Autoimmunity and Inflammation Program, Hospital for Special Surgery, New York, NY 10021; .,Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065.,Pediatric Rheumatology, Hospital for Special Surgery, New York, NY 10021
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21
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Shirani K, Iranshahi M, Askari VR, Gholizadeh Z, Zadeh AA, Zeinali M, Hassani FV, Taherzadeh Z. Comparative evaluation of the protective effects of oral administration of auraptene and umbelliprenin against CFA-induced chronic inflammation with polyarthritis in rats. Biomed Pharmacother 2021; 139:111635. [PMID: 34243601 DOI: 10.1016/j.biopha.2021.111635] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 04/13/2021] [Accepted: 04/19/2021] [Indexed: 12/20/2022] Open
Abstract
This study aimed to evaluate the anti-inflammatory effect of Auraptene (AUR) and Umbelliprenin (UMB) in a rat model of rheumatoid arthritis (RA) induced by using complete Freund's adjuvant (CFA). Paw swelling of adjuvant arthritis rats measured at various times after CFA injection. Over 15 days of RA induction, mediator/cytokine-mediated processes involved in managing the regulation and resolving RA's inflammation were also quantified with ELISA. Histopathological changes were also assessed under a microscope 15 days after the CFA injection. AUR at all doses and UMB administration only at a 16 mM /kg administration dose significantly reduced CFA-induced paw edema level compared to the control group. UMB (64 and 32 mM) and AUR (64, 32, and 16 mM) could reduce the PGE2 (p < .0001-.01) and NO (p < .0001-.05) levels in the treatment groups compared to the negative control group. However, these compounds showed no significant effect on the TNF-α, IFN-γ, TGF-β, IL-4, and IL-10 levels than the control group (p > .05). Unlike indomethacin and prednisolone, treatment of rats with AUR (16, 32, and 64 mM/kg) and UMB (16 and 32 mM/kg) reduced the level of IL-2 (p < .0001). In all treatment groups, the serum level of IL-17 was significantly reduced compared to the CFA group (p < .001-0.05). We suggested AUR and UMB could diminish inflammation by reducing the serum level of IL-17 and could be considered a proper alternative in the treatment of IL-17 related inflammatory diseases such as rheumatoid arthritis. Given that AUR and UMB apply their anti-inflammatory effects by changing distinct cytokine release/inhibition patterns, their potential application in diverse inflammatory diseases seems different.
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Affiliation(s)
- Kobra Shirani
- Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Mehrdad Iranshahi
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Vahid Reza Askari
- Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Persian Medicine, School of Persian and Complementary Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Zahra Gholizadeh
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Armin Attaran Zadeh
- Department of Medical Genetics, Faculty of Medicines, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Majid Zeinali
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Zhila Taherzadeh
- Targeted Drug Delivery Research Center, Mashhad University of Medical Sciences, P.O. Box: 1365-91775, Mashhad, Iran.
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22
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Monfort JB, Chasset F, Barbaud A, Frances C, Senet P. Nailfold capillaroscopy findings in cutaneous lupus erythematosus patients with or without digital lesions and comparison with dermatomyositis patients: A prospective study. Lupus 2021; 30:1207-1213. [PMID: 33853419 DOI: 10.1177/09612033211010329] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Differential diagnosis between cutaneous lupus erythematosus (CLE) and dermatomyositis (DM) may be challenging if digital lesions occur. OBJECTIVES To compare nailfold capillaroscopy (NFC) findings in CLE patients with or without digital involvement, and to compare capillaroscopic findings between CLE patients with digital lesions and DM patients. METHODS Prospective monocentric study including CLE and DM patients. NFC was performed and standardized items were recorded. RESULTS Fifty-one CLE patients and 10 DM patients with digital lesions were included. A scleroderma pattern was found in 6 patients (12%): in 5 out of 17 patients with digital lesions, compared with only 1 out of 34 patients without digital lesions (p = 0.01). In multivariate analysis, CLE digital lesions and digital ulcerations were statistically associated with scleroderma pattern. CLE digital lesions were significantly associated with architectural disorganization (p = 0.0003) and capillary rarefaction (p = 0.0038). A scleroderma pattern was significantly more frequent in DM patients (80%) than in CLE patients with digital lesions (30%, p = 0.018). Capillaroscopic findings were not significantly different between CLE patients with digital lesions and DM patients. CONCLUSION Although scleroderma pattern is more frequent in DM patients than in CLE patients with digital lesions, NFC cannot formally distinguish CLE from DM.
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Affiliation(s)
- Jean-Benoît Monfort
- Sorbonne Université, Faculté de Médecine Sorbonne Université, AP-HP, Service de Dermatologie et Allergologie, Hôpital Tenon, F-75020 Paris, France
| | - François Chasset
- Sorbonne Université, Faculté de Médecine Sorbonne Université, AP-HP, Service de Dermatologie et Allergologie, Hôpital Tenon, F-75020 Paris, France
| | - Annick Barbaud
- Sorbonne Université, Faculté de Médecine Sorbonne Université, AP-HP, Service de Dermatologie et Allergologie, Hôpital Tenon, F-75020 Paris, France
| | - Camille Frances
- Sorbonne Université, Faculté de Médecine Sorbonne Université, AP-HP, Service de Dermatologie et Allergologie, Hôpital Tenon, F-75020 Paris, France
| | - Patricia Senet
- Sorbonne Université, Faculté de Médecine Sorbonne Université, AP-HP, Service de Dermatologie et Allergologie, Hôpital Tenon, F-75020 Paris, France
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23
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Comedonic Lupus: An Unusual Presentation of Cutaneous Lupus. ACTAS DERMO-SIFILIOGRAFICAS 2021. [DOI: 10.1016/j.adengl.2021.01.038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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24
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Rajamohanan R, Koshy S, Ganguly S, Ramdas A, Kuruvila S. Atypical cutaneous manifestations in lupus erythematosus: A report of three cases. JOURNAL OF CURRENT RESEARCH IN SCIENTIFIC MEDICINE 2021. [DOI: 10.4103/jcrsm.jcrsm_35_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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25
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Chanprapaph K, Tankunakorn J, Suchonwanit P, Rutnin S. Dermatologic Manifestations, Histologic Features and Disease Progression among Cutaneous Lupus Erythematosus Subtypes: A Prospective Observational Study in Asians. Dermatol Ther (Heidelb) 2020; 11:131-147. [PMID: 33280074 PMCID: PMC7859020 DOI: 10.1007/s13555-020-00471-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Accepted: 11/21/2020] [Indexed: 01/19/2023] Open
Abstract
Introduction Cutaneous manifestations are central to the primary diagnosis of systemic lupus erythematosus (SLE). However, information on the clinical, histopathologic, and direct immunofluorescence (DIF) features among subtypes of cutaneous lupus erythematosus (CLE), as well as longitudinal prospective observational study to evaluate the natural history and the progression to SLE, is lacking among Asians. Our objectives are to summarize the differences in the clinical, histopathologic, and DIF characteristics and serological profiles between various subtypes of CLE, and to provide its natural history and the association with disease activity in our Asian population. Methods A prospective observational study on CLE patients was performed between May 2016 and May 2020. Patients underwent full physical/dermatologic examination, skin biopsy for histology, and DIF. Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores and laboratory data were evaluated. Time schedule and characteristics for resolution and/or the disease progression to SLE were recorded in subsequent follow-ups. Results Of 101 biopsy-proven CLE patients, 25 had acute CLE (ACLE), 8 had subacute CLE (SCLE), 39 had chronic CLE (CCLE) only, 22 had CCLE with SLE, and 7 had LE-nonspecific cutaneous lesions only. Patients with exclusive CLE showed lower female preponderance, serological abnormalities, and correlation to systemic disease. However, when CLE was accompanied with any LE-nonspecific cutaneous manifestations, they were associated with high antinuclear antibody (ANA) titer, renal, hematologic, joint involvement, and greater SLEDAI score. Of 207 biopsy sections, SCLE/CCLE regardless of systemic involvement showed significantly higher percentage of superficial/deep perivascular and perieccrine infiltration than ACLE. On DIF, deposition of multiple immunoreactants was associated with higher systemic disease. Approximately 10% of CLE-only patients later developed SLE but had mild systemic involvement. Conclusion Our findings support that each CLE subtype has a diverse and unique character. Comprehensive understanding of the differences among CLE subtypes is important for achieving the correct diagnosis and providing appropriate disease monitoring and management. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-020-00471-y.
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Affiliation(s)
- Kumutnart Chanprapaph
- Division of Dermatology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Jutamas Tankunakorn
- Division of Dermatology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Poonkiat Suchonwanit
- Division of Dermatology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Suthinee Rutnin
- Division of Dermatology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
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26
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Chessé C, Fernández-Tapia MJ, Borzotta F. Comedonic Lupus: An Unusual Presentation of Cutaneous Lupus. ACTAS DERMO-SIFILIOGRAFICAS 2020; 112:370-371. [PMID: 33130011 DOI: 10.1016/j.ad.2019.07.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Revised: 06/21/2019] [Accepted: 07/14/2019] [Indexed: 12/01/2022] Open
Affiliation(s)
- C Chessé
- Servicio de dermatología, Hospital Luis C Lagomaggiore, Mendoza, Argentina.
| | | | - F Borzotta
- Servicio de dermatología, Hospital Luis C Lagomaggiore, Mendoza, Argentina
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27
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Lu JQ, Popovic S, Provias J, Cenic A. Collision Lesions of Calcifying Pseudoneoplasm of the Neuraxis and Rheumatoid Nodules: A Case Report With New Pathogenic Insights. Int J Surg Pathol 2020; 29:314-320. [PMID: 32666850 DOI: 10.1177/1066896920941939] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumor-like lesion with unclear pathogenesis. Collision lesions of CAPNONs with neoplasms are occasionally reported. In this article, we report the first case of collision lesions between CAPNON and rheumatoid nodules (RNs) in a patient with systemic lupus erythematosus. The patient was a 51-year-old female who presented with lower back pain and subsequently a lower back mass over 2 years. Spinal magnetic resonance imaging demonstrated a heterogeneous, partially calcified mass centered in the L3-4 paravertebral regions. A biopsy of the mass was diagnostic of CAPNON. As the mass grew over the following 5 months, it was resected en bloc. Its pathological examination revealed collision lesions of RNs at different histopathological stages and CAPNON lesions, and transitional lesions exhibiting combined RN and CAPNON features, with immune cell infiltrates. Our findings provide new evidence for an immune-mediated reactive process and insights into the pathogenies of CAPNON.
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Affiliation(s)
| | | | - John Provias
- 3710McMaster University, Hamilton, Ontario, Canada
| | - Aleksa Cenic
- 3710McMaster University, Hamilton, Ontario, Canada
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Domingo S, Solé C, Moliné T, Ferrer B, Ordi-Ros J, Cortés-Hernández J. Efficacy of Thalidomide in Discoid Lupus Erythematosus: Insights into the Molecular Mechanisms. Dermatology 2020; 236:467-476. [PMID: 32659758 DOI: 10.1159/000508672] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Accepted: 05/11/2020] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Thalidomide has been used successfully in a variety of chronic refractory inflammatory dermatological conditions with underlying autoimmune or infectious pathogenesis. It was first used for refractory discoid lupus erythematosus (DLE) in 1983 and has steadily grown since then. METHOD In this review, we describe the therapeutic benefits of thalidomide for DLE treatment and its biological properties. We explain how new discoveries in DLE pathogenesis are relevant to understand thalidomide's mechanism of action and the need to find an alternative safe drug with similar therapeutic effects. SUMMARY Thalidomide's efficacy in DLE patients is significant, with 80-90% reaching clinical remission according to different studies. However, thalidomide's use is still limited by serious adverse effects such as teratogenicity, neurotoxicity, and thrombosis. In addition, there is a frequent rate of relapse and many patients require a long-term low dose of thalidomide as maintenance. The achievement of clinical response within weeks is key to avoid irreversible DLE fibrotic sequelae, making it critical to introduce thalidomide earlier in the DLE treatment algorithm. Recently, microarray and miRNA screenings demonstrated a significant CD4+ T enrichment and T-helper 1 response predom-inance with a dysregulation of regulatory T cell (Treg) expression in DLE lesions that induced high levels of proinflammatory, chemotaxis, and apoptotic proteins that induce the chronic inflammation response. Thalidomide's anti-inflammatory, antiangiogenic, and T-cell co-stimulatory effects may be beneficial for DLE since it promotes cytokine inhibition, inhibits macrophage activation, regulates Treg responses, inhibits angiogenesis, modulates T cells, and promotes NK cell-mediated cytotoxicity.
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Affiliation(s)
- Sandra Domingo
- Rheumatology Research Group, Lupus Unit, Vall d'Hebron University Hospital, Vall d´Hebron Research Institute (VHIR), Barcelona, Spain
| | - Cristina Solé
- Rheumatology Research Group, Lupus Unit, Vall d'Hebron University Hospital, Vall d´Hebron Research Institute (VHIR), Barcelona, Spain,
| | - Teresa Moliné
- Departament of Pathology, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Berta Ferrer
- Departament of Pathology, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Josep Ordi-Ros
- Department of Internal Medicine, Vall d'Hebron University Hospital, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain
| | - Josefina Cortés-Hernández
- Rheumatology Research Group, Lupus Unit, Vall d'Hebron University Hospital, Vall d´Hebron Research Institute (VHIR), Barcelona, Spain
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29
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Garelli CJ, Refat MA, Nanaware PP, Ramirez-Ortiz ZG, Rashighi M, Richmond JM. Current Insights in Cutaneous Lupus Erythematosus Immunopathogenesis. Front Immunol 2020; 11:1353. [PMID: 32714331 PMCID: PMC7343764 DOI: 10.3389/fimmu.2020.01353] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 05/27/2020] [Indexed: 12/25/2022] Open
Abstract
Cutaneous Lupus Erythematosus (CLE) is a clinically diverse group of autoimmune skin diseases with shared histological features of interface dermatitis and autoantibodies deposited at the dermal-epidermal junction. Various genetic and environmental triggers of CLE promote infiltration of T cells, B cells, neutrophils, antigen presenting cells, and NK cells into lesional skin. In this mini-review, we will discuss the clinical features of CLE, insights into CLE immunopathogenesis, and novel treatment approaches.
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Affiliation(s)
- Colton J. Garelli
- Department of Dermatology, University of Massachusetts Medical School, Worcester, MA, United States
| | - Maggi Ahmed Refat
- Department of Dermatology, University of Massachusetts Medical School, Worcester, MA, United States
| | - Padma P. Nanaware
- Department of Pathology, University of Massachusetts Medical School, Worcester, MA, United States
| | - Zaida G. Ramirez-Ortiz
- Department of Medicine, University of Massachusetts Medical School, Worcester, MA, United States
| | - Mehdi Rashighi
- Department of Dermatology, University of Massachusetts Medical School, Worcester, MA, United States
| | - Jillian M. Richmond
- Department of Dermatology, University of Massachusetts Medical School, Worcester, MA, United States
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30
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Obermoser G, Zelger B, Zelger B. [Lupus erythematosus-a clinico-pathological heterogeneous disease]. DER PATHOLOGE 2020; 41:334-343. [PMID: 32347330 DOI: 10.1007/s00292-020-00785-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Lupus erythematosus (LE) is an autoimmune disorder where immune tolerance towards nucleic acids is lost and a hyperactivated type I interferon system drives chronic immune activation. Typically, signs, symptoms, and clinical disease course are very variable between patients. Cutaneous LE can be associated with or precede systemic involvement or be limited to the skin, necessitating careful examination and follow-up of patients. LE skin disease includes a wide range of manifestations and precise classification for clinical studies is challenging. In this review article we discuss common and rare manifestations of cutaneous lupus with its clinical presentation and histopathological characteristics.
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Affiliation(s)
| | - Bettina Zelger
- Institut für Pathologie, Medizinische Universität Innsbruck, Innsbruck, Österreich
| | - Bernhard Zelger
- Universitätsklinik für Dermatologie, Venerologie und Allergologie, Medizinische Universität Innsbruck, Anichstraße 35, 6020, Innsbruck, Österreich.
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31
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Update on vasculitis: an overview and dermatological clues for clinical and histopathological diagnosis - part I. An Bras Dermatol 2020; 95:355-371. [PMID: 32307202 PMCID: PMC7253914 DOI: 10.1016/j.abd.2020.01.003] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2019] [Accepted: 01/19/2020] [Indexed: 11/22/2022] Open
Abstract
The term vasculitis refers to the inflammation of vessel walls. It may range in severity from a self-limited disorder in one single organ to a life-threatening disease due to multiple organ failure. It has many causes, although they result in only a few histological patterns of vascular inflammation. Vessels of any type and in any organ can be affected, a fact that results in a broad variety of signs and symptoms. Different vasculitides with indistinguishable clinical presentations have quite different prognosis and treatments. This condition presents many challenges to physicians in terms of classification, diagnosis, appropriate laboratory workup, and treatment. Moreover, it compels a careful follow-up. This article reviews the Chapel-Hill 2012 classification, etiology, recent insights in pathophysiology, some important dermatological clues for the diagnosis and summarizes treatment of some of these complex vasculitis syndromes.
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32
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Esteves M, Lopes S, Santos P, Azevedo F. Vesiculobullous subacute cutaneous lupus erythematosus: A rare presentation. Indian Dermatol Online J 2020; 11:446-448. [PMID: 32695716 PMCID: PMC7367580 DOI: 10.4103/idoj.idoj_341_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 12/28/2019] [Accepted: 12/29/2019] [Indexed: 11/05/2022] Open
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Patsinakidis N, Kautz O, Gibbs BF, Raap U. Lupus erythematosus tumidus: clinical perspectives. Clin Cosmet Investig Dermatol 2019; 12:707-719. [PMID: 31632119 PMCID: PMC6778445 DOI: 10.2147/ccid.s166723] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2019] [Accepted: 07/05/2019] [Indexed: 12/13/2022]
Abstract
Lupus erythematosus tumidus (LET) is an uncommon and photosensitive inflammatory skin disorder which is characterised by erythematous urticarial plaques. In the last 20 years, extensive research on clinical and histological aspects of the disease have led to a better characterization of this nosological entity and to differentiate it from other similar or related diseases. Today, LET is considered as a separate subtype of cutaneous lupus erythematosus (CLE) with a benign, intermittent clinical course (intermittent CLE, ICLE) and only rarely associated with systemic lupus erythematosus (SLE).
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Affiliation(s)
- Nikolaos Patsinakidis
- University Clinic of Dermatology and Allergology, University of Oldenburg, Klinikum Oldenburg Aör, Oldenburg, Germany.,Division of Experimental Allergy and Immunodermatology, University of Oldenburg, Oldenburg, Germany
| | - Ocko Kautz
- University Clinic of Dermatology and Allergology, University of Oldenburg, Klinikum Oldenburg Aör, Oldenburg, Germany
| | - Bernhard F Gibbs
- Division of Experimental Allergy and Immunodermatology, University of Oldenburg, Oldenburg, Germany
| | - Ulrike Raap
- University Clinic of Dermatology and Allergology, University of Oldenburg, Klinikum Oldenburg Aör, Oldenburg, Germany.,Division of Experimental Allergy and Immunodermatology, University of Oldenburg, Oldenburg, Germany
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34
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Cutaneous lupus erythematosus: new insights into pathogenesis and therapeutic strategies. Nat Rev Rheumatol 2019; 15:519-532. [PMID: 31399711 DOI: 10.1038/s41584-019-0272-0] [Citation(s) in RCA: 116] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/08/2019] [Indexed: 01/07/2023]
Abstract
Cutaneous lupus erythematosus (CLE) is an autoimmune disease that can present as an isolated skin disease or as a manifestation within the spectrum of systemic lupus erythematosus. The clinical spectrum of CLE is broad, ranging from isolated discoid plaques to widespread skin lesions. Histologically, skin lesions present as interface dermatitis (inflammation of the skin mediated by anti-epidermal responses), which is orchestrated by type I and type III interferon-regulated cytokines and chemokines. Both innate and adaptive immune pathways are strongly activated in the formation of skin lesions owing to continuous re-activation of innate pathways via pattern recognition receptors (PRRs). These insights into the molecular pathogenesis of skin lesions in CLE have improved our understanding of the mechanisms underlying established therapies and have triggered the development of targeted treatment strategies that focus on immune cells (for example, B cells, T cells or plasmacytoid dendritic cells), as well as immune response pathways (for example, PRR signalling, Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signalling and nuclear factor-κB signalling) and their cytokines and chemokines (for example, type I interferons, CXC-chemokine ligand 10 (CXCL10), IL-6 and IL-12).
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35
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Blake SC, Daniel BS. Cutaneous lupus erythematosus: A review of the literature. Int J Womens Dermatol 2019; 5:320-329. [PMID: 31909151 PMCID: PMC6938925 DOI: 10.1016/j.ijwd.2019.07.004] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 07/04/2019] [Accepted: 07/20/2019] [Indexed: 02/06/2023] Open
Abstract
Knowledge with regard to the pathogenesis of lupus erythematosus has progressed rapidly over the past decade, and with it has come promising new agents for the treatment of cutaneous lupus erythematous (CLE). Classification of CLE is performed using clinical features and histopathologic findings, and is crucial for determining prognosis and choosing therapeutic options. Preventative therapy is critical in achieving optimal disease control, and patients should be counseled on sun-safe behavior and smoking cessation. First-line therapy includes topical corticosteroids and calcineurin inhibitors, with antimalarial therapy. Traditionally, refractory disease was treated with oral retinoids, dapsone, and other oral immunosuppressive drugs, but new therapies are emerging with improved side effect profiles and efficacy. Biologic agents, such as belimumab and ustekinumab, have been promising in case studies but will require larger trials to establish their role in routine therapy. Other novel therapies that have been trialed successfully include spleen tyrosine kinase inhibitors and fumaric acid esters. Finally, new evidence has been published recently that describes safer dosing regimens in thalidomide and lenalidomide, both effective medications for CLE. Given the chronic disease course of CLE, long-term treatment-related side effects must be minimized, and the introduction of new steroid-sparing agents is encouraging in this regard.
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Affiliation(s)
- Stephanie Clare Blake
- University of New South Wales, Sydney, Australia.,St. George Department of Dermatology, Sydney, Australia
| | - Benjamin Silas Daniel
- University of New South Wales, Sydney, Australia.,St. George Department of Dermatology, Sydney, Australia.,St Vincent's Hospital, Melbourne, Australia
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36
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Michot JM, Fusellier M, Champiat S, Velter C, Baldini C, Voisin AL, Danlos FX, Dakdouki YE, Annereau M, Mariette X, Robert C, Cherif K, Marabelle A, Mateus C, Lambotte O. Drug-induced lupus erythematosus following immunotherapy with anti-programmed death-(ligand) 1. Ann Rheum Dis 2019; 78:e67. [PMID: 29858173 DOI: 10.1136/annrheumdis-2018-213677] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2018] [Accepted: 05/01/2018] [Indexed: 11/04/2022]
Affiliation(s)
- Jean-Marie Michot
- Medical Oncology and Drug Development Department, Institut Gustave Roussy, Villejuif, France
- Department of Internal Medicine and Clinical Immunology, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - Mathilde Fusellier
- Medical Oncology and Drug Development Department, Institut Gustave Roussy, Villejuif, France
| | - Stephane Champiat
- Medical Oncology and Drug Development Department, Institut Gustave Roussy, Villejuif, France
- University of Paris Sud, Le Kremlin-Bicêtre, France
| | - Charles Velter
- Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France
| | - Capucine Baldini
- Medical Oncology and Drug Development Department, Institut Gustave Roussy, Villejuif, France
- University of Paris Sud, Le Kremlin-Bicêtre, France
| | - Anne-Laure Voisin
- Department of Pharmacovigilance, Institut Gustave Roussy, Villejuif, France
| | - Francois-Xavier Danlos
- Medical Oncology and Drug Development Department, Institut Gustave Roussy, Villejuif, France
| | - Yolla El Dakdouki
- Medical Oncology and Drug Development Department, Institut Gustave Roussy, Villejuif, France
| | - Maxime Annereau
- Department of Pharmacy, Institut Gustave Roussy, Villejuif, France
| | - Xavier Mariette
- Department of Rheumatology, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
| | - Caroline Robert
- Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France
| | - Khadija Cherif
- Department of Biopathology, Institut Gustave Roussy, Villejuif, France
| | - Aurélien Marabelle
- Medical Oncology and Drug Development Department, Institut Gustave Roussy, Villejuif, France
| | - Christine Mateus
- Department of Medical Oncology, Institut Gustave Roussy, Villejuif, France
| | - Olivier Lambotte
- Department of Internal Medicine and Clinical Immunology, Hôpital Bicêtre, Le Kremlin-Bicêtre, France
- University of Paris Sud, Le Kremlin-Bicêtre, France
- INSERM U1184, Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin- Bicêtre, France
- Commissariat à l'Energie Atomique (CEA), Fontenay-aux-Roses, France
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37
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Fernandes M, Taulaigo AV, Vidal C, Agostini P, Riso N, Moraes‐Fontes MF. Heterogeneous lupus-specific lesions and treatment outcome, in a single patient, over a period of time. Clin Case Rep 2019; 7:865-871. [PMID: 31110705 PMCID: PMC6509922 DOI: 10.1002/ccr3.2105] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Revised: 02/25/2019] [Accepted: 02/27/2019] [Indexed: 01/26/2023] Open
Abstract
The report highlights the importance of strict clinico-histological correlations when skin biopsies are performed in diagnostic doubt in systemic lupus erythematosus. Furthermore, PUVA is never indicated in autoimmune conditions involving photosensitivity, due to high potential for internal and cutaneous aggravation of the disease, as the authors observed in this case.
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Affiliation(s)
- Melissa Fernandes
- Unidade de Doenças Auto-imunes/Serviço de Medicina 7.2, Hospital de Curry CabralCentro Hospitalar Universitário de Lisboa CentralLisboaPortugal
| | - Anna V. Taulaigo
- Unidade de Doenças Auto-imunes/Serviço de Medicina 7.2, Hospital de Curry CabralCentro Hospitalar Universitário de Lisboa CentralLisboaPortugal
| | - Carolina Vidal
- Unidade de Doenças Auto-imunes/Serviço de Medicina 7.2, Hospital de Curry CabralCentro Hospitalar Universitário de Lisboa CentralLisboaPortugal
- Serviço de Medicina InternaHospital do Divino Espírito SantoPonta Delgada, AçoresPortugal
| | - Patrick Agostini
- Laboratório de Anatomia PatológicaCentro Hospitalar Universitário do AlgarveFaro‐PortimãoPortugal
| | - Nuno Riso
- Unidade de Doenças Auto-imunes/Serviço de Medicina 7.2, Hospital de Curry CabralCentro Hospitalar Universitário de Lisboa CentralLisboaPortugal
| | - Maria Francisca Moraes‐Fontes
- Unidade de Doenças Auto-imunes/Serviço de Medicina 7.2, Hospital de Curry CabralCentro Hospitalar Universitário de Lisboa CentralLisboaPortugal
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38
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Richmond JM, Strassner JP, Essien KI, Harris JE. T-cell positioning by chemokines in autoimmune skin diseases. Immunol Rev 2019; 289:186-204. [PMID: 30977191 PMCID: PMC6553463 DOI: 10.1111/imr.12762] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Revised: 03/18/2019] [Accepted: 03/21/2019] [Indexed: 12/12/2022]
Abstract
Autoimmune skin diseases are complex processes in which autoreactive cells must navigate through the skin tissue to find their targets. Regulatory T cells in the skin help to mitigate autoimmune inflammation and may in fact be responsible for the patchy nature of these conditions. In this review, we will discuss chemokines that are important for global recruitment of T cell populations to the skin during disease, as well as signals that fine-tune their localization and function. We will describe prototypical disease responses and chemokine families that mediate these responses. Lastly, we will include an overview of chemokine-targeting drugs that have been tested as new treatment strategies for autoimmune skin diseases.
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Affiliation(s)
- Jillian M Richmond
- Department of Dermatology, UMass Medical School, Worcester, Massachusetts
| | - James P Strassner
- Department of Dermatology, UMass Medical School, Worcester, Massachusetts
| | - Kingsley I Essien
- Department of Dermatology, UMass Medical School, Worcester, Massachusetts
| | - John E Harris
- Department of Dermatology, UMass Medical School, Worcester, Massachusetts
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39
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Lu J, Zhang L, Sun X, Wang Z. Stevens-Johnson syndrome in systemic lupus erythematosus. Assoc Med J 2019. [DOI: 10.1136/bmj.l1257] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
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40
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41
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Drenkard C, Parker S, Aspey LD, Gordon C, Helmick CG, Bao G, Lim SS. Racial Disparities in the Incidence of Primary Chronic Cutaneous Lupus Erythematosus in the Southeastern US: The Georgia Lupus Registry. Arthritis Care Res (Hoboken) 2019; 71:95-103. [PMID: 29669194 PMCID: PMC6193862 DOI: 10.1002/acr.23578] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Accepted: 04/10/2018] [Indexed: 01/17/2023]
Abstract
OBJECTIVE Relative to studies of systemic lupus erythematosus (SLE), epidemiologic studies of chronic cutaneous lupus erythematosus (CCLE) are rare and are limited to populations with no racial diversity. We sought to provide minimum estimates of the incidence of primary CCLE (CCLE in the absence of SLE) in a population comprised predominantly of white individuals and black individuals in the southeastern region of the US. METHODS The Georgia Lupus Registry allowed for the use of multiple sources for case-finding, including dermatology and rheumatology practices, multispecialty health care facilities, and dermatopathology reports. Cases with a clinical or clinical/histologic diagnosis of CCLE were classified as definite. Cases ascertained exclusively from dermatopathology reports were categorized as probable. Age-standardized incidence rates stratified by sex and race were calculated for discoid lupus erythematosus (DLE) in particular and for CCLE in general. RESULTS The overall age-adjusted estimates for combined (definite and probable) CCLE were 3.9 per 100,000 person-years (95% confidence interval [95% CI] 3.4-4.5). The overall age-adjusted incidences of definite and combined DLE were 2.9 (95% CI 2.4-3.4) and 3.7 (95% CI 3.2-4.3) per 100,000 person-years, respectively. When capture-recapture methods were used, the age-adjusted incidence of definite DLE increased to 4.0 (95% CI 3.2-4.3). The black:white and female:male incidence ratios for definite DLE were 5.4 and 3.1, respectively. CONCLUSION Our findings underscore the striking racial disparities in susceptibility to primary CCLE, with black individuals having a 3-fold to 5-fold increased incidence of CCLE in general, and DLE in particular, compared with white individuals. The observed sex differences were consistent with those reported previously, with a 3 times higher risk of DLE in women compared with men.
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Affiliation(s)
- Cristina Drenkard
- Emory University, Department of Medicine, Division of Rheumatology, Atlanta, Georgia, US
| | - Sareeta Parker
- Kaiser Permanente, Department of Dermatology, Jonesboro, Georgia, US
| | - Laura D. Aspey
- Emory University School of Medicine, Department of Dermatology, Atlanta, Georgia, US
| | - Caroline Gordon
- Rheumatology Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom
| | - Charles G. Helmick
- Arthritis Program, Centers for Disease Control and Prevention, Atlanta, Georgia, US
| | - Gaobin Bao
- Emory University, Department of Medicine, Division of Rheumatology, Atlanta, Georgia, US
| | - S. Sam Lim
- Emory University, Department of Medicine, Division of Rheumatology, Atlanta, Georgia, US
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42
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Barron AMS, Mantero JC, Ho JD, Nazari B, Horback KL, Bhawan J, Lafyatis R, Lam C, Browning JL. Perivascular Adventitial Fibroblast Specialization Accompanies T Cell Retention in the Inflamed Human Dermis. THE JOURNAL OF IMMUNOLOGY 2018; 202:56-68. [PMID: 30510068 DOI: 10.4049/jimmunol.1801209] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/31/2018] [Accepted: 10/29/2018] [Indexed: 12/12/2022]
Abstract
Perivascular accumulation of lymphocytes can be a prominent histopathologic feature of various human inflammatory skin diseases. Select examples include systemic sclerosis, spongiotic dermatitis, and cutaneous lupus. Although a large body of work has described various aspects of the endothelial and vascular smooth muscle layers in these diseases, the outer adventitial compartment is poorly explored. The goal of the current study was to characterize perivascular adventitial fibroblast states in inflammatory human skin diseases and relate these states to perivascular lymphocyte accumulation. In normal skin, adventitial fibroblasts are distinguished by CD90 expression, and dense perivascular lymphocytic infiltrates are uncommon. In systemic sclerosis, this compartment expands, but lymphocyte infiltrates remain sparse. In contrast, perivascular adventitial fibroblast expression of VCAM1 is upregulated in spongiotic dermatitis and lupus and is associated with a dense perivascular T cell infiltrate. VCAM1 expression marks transitioned fibroblasts that show some resemblance to the reticular stromal cells in secondary lymphoid organs. Expanded adventitial compartments with perivascular infiltrates similar to the human settings were not seen in the inflamed murine dermis. This species difference may hinder the dissection of aspects of perivascular adventitial pathology. The altered perivascular adventitial compartment and its associated reticular network form a niche for lymphocytes and appear to be fundamental in the development of an inflammatory pattern.
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Affiliation(s)
- Alexander M S Barron
- Department of Microbiology, Boston University School of Medicine, Boston, MA 02118
| | - Julio C Mantero
- Department of Microbiology, Boston University School of Medicine, Boston, MA 02118
| | - Jonathan D Ho
- Department of Dermatology, Boston University School of Medicine, Boston, MA 02118
| | - Banafsheh Nazari
- Section of Rheumatology, Boston University School of Medicine, Boston, MA 02118
| | - Katharine L Horback
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115; and
| | - Jag Bhawan
- Department of Dermatology, Boston University School of Medicine, Boston, MA 02118
| | - Robert Lafyatis
- Section of Rheumatology, Boston University School of Medicine, Boston, MA 02118.,Division of Rheumatology and Clinical Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213
| | - Christina Lam
- Department of Dermatology, Boston University School of Medicine, Boston, MA 02118
| | - Jeffrey L Browning
- Department of Microbiology, Boston University School of Medicine, Boston, MA 02118; .,Section of Rheumatology, Boston University School of Medicine, Boston, MA 02118
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Chasset F, Richez C, Martin T, Belot A, Korganow AS, Arnaud L. Rare diseases that mimic Systemic Lupus Erythematosus (Lupus mimickers). Joint Bone Spine 2018; 86:165-171. [PMID: 30837156 DOI: 10.1016/j.jbspin.2018.10.007] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/22/2018] [Indexed: 12/13/2022]
Abstract
Several conditions have clinical and laboratory features that can mimic those present in Systemic Lupus Erythematosus (SLE). Some of these "SLE mimickers" are very common, such as rosacea which can be mistaken for the butterfly rash, while others such as Kikuchi disease, type-1 interferonopathies, Castleman's disease, prolidase deficiency, angioimmunoblastic T-cell lymphoma, Evans' syndrome in the context of primary immune deficiencies and the autoimmune lymphoproliferative syndrome are exceptionally uncommon. A proper diagnosis of SLE must therefore be based upon a complete medical history as well as on the adequate constellation of clinical or laboratory findings. While there is no single test that determines whether a patient has lupus or not, the search for auto-antibodies towards nuclear antigens is a key step in the diagnosis strategy, keeping in mind that ANAs are not specific for SLE. In case of persistent doubt, patients should be referred to reference centers with experience in the management of the disease.
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Affiliation(s)
- François Chasset
- Service de dermatologie et d'allergologie, hôpital Tenon, AP-HP, 75020, Paris, France
| | - Christophe Richez
- Immunoconcept, CNRS-UMR 5164, université de Bordeaux, 146, rue Léo-Saignat, 33076, Bordeaux, France; Centre hospitalier universitaire de Bordeaux, FHU ACRONIM, place Amélie-Raba-Léon, 33076, Bordeaux, France; Centre national de référence des maladies autoimmunes et systémiques rares Est Sud-Ouest (RESO)-LUPUS, 67000 Strasbourg, France
| | - Thierry Martin
- Centre national de référence des maladies autoimmunes et systémiques rares Est Sud-Ouest (RESO)-LUPUS, 67000 Strasbourg, France; Service d'immunologie clinique nouvel hôpital civil, 1, place de l'hôpital 67091 Strasbourg cedex, France
| | - Alexandre Belot
- Service de nephrologie, rhumatologie et dermatologie pédiatriques, hôpital Femme Mère-Enfant, hospices civils de Lyon, Lyon, France; Université de Lyon, 59, boulevard Pinel, 69677 Bron cedex, France; Inserm U1111, 69007 Lyon, France; Filière des maladies autoimmunes et autoinflammatoires rares (FAI2R), 69677 Lyon, France
| | - Anne-Sophie Korganow
- Centre national de référence des maladies autoimmunes et systémiques rares Est Sud-Ouest (RESO)-LUPUS, 67000 Strasbourg, France; Service d'immunologie clinique nouvel hôpital civil, 1, place de l'hôpital 67091 Strasbourg cedex, France
| | - Laurent Arnaud
- Centre national de référence des maladies autoimmunes et systémiques rares Est Sud-Ouest (RESO)-LUPUS, 67000 Strasbourg, France; Service de rhumatologie, hôpitaux universitaires de Strasbourg, 67098 Strasbourg, France; Université de Strasbourg, Inserm UMR-S 1109, 67000 Strasbourg, France.
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Sibanda EN, Chase-Topping M, Pfavayi LT, Woolhouse MEJ, Mutapi F. Evidence of a distinct group of Black African patients with systemic lupus erythematosus. BMJ Glob Health 2018; 3:e000697. [PMID: 30245865 PMCID: PMC6144901 DOI: 10.1136/bmjgh-2017-000697] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Revised: 04/23/2018] [Accepted: 04/27/2018] [Indexed: 12/17/2022] Open
Abstract
Background The autoimmune disease systemic lupus erythematosus (SLE) occurs more frequently in patients of African descent with high morbidity and mortality. Current SLE diagnostic criteria including antinuclear antibody (ANA) reactivity are derived largely from non-African populations. This study characterises ANA reactivity patterns and relates them to SLE clinical presentation in Black African patients. Methods Sera from Black participants (61 patients with SLE and 100 controls) aged 1-81 years were analysed for reactivity against the antigens: uridine 1-ribonuclear protein, Smith uridine-1-5 ribonuclear protein antigen, soluble substance-A, recombinant Ro-52, soluble substance-B, Scl-70, cytoplasmic histidyl-tRNA synthetase antigen, proliferating cell nuclear antigen (PCNA), nucleosomes, ribonuclear P-protein, antimitochondrial antibody M2 (AMA-M2), histones, double-stranded DNA (dsDNA), centromere protein B and polymyositis-sclerosis overlap antigen. Findings A significantly higher proportion (97%) of the 61 patients with SLE had detectable autoantibody reactivity compared with 15% of the 100 controls (p<0.001). The highest frequencies of autoantibody reactivity in patients with SLE were against the dsDNA antigen (41%) and PCNA (54%). Anti-PCNA and anti-dsDNA reactivity were mutually exclusive (p<0.001) giving rise to two distinct groups of Black African patients with SLE. The first group (n=25) had reactivity profiles consistent with international standard SLE definitions, including anti-dsDNA reactivity, and was 13 times more likely to present with joint symptoms. The larger, second group (n=34), characterised by anti-PCNA and anti-AMA-M2 reactivity, was nine times more likely to present with only cutaneous symptoms. Interpretation Our study demonstrates a need to extend autoantibody panels to include anti-PCNA in the diagnostic process of Black African patients and further refine the predictive values of the reactivity to different antigens to differentiate SLE syndromes in African populations.
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Affiliation(s)
- Elopy N Sibanda
- Asthma, Allergy and Immunology Clinic, Twin Palms Medical Centre, Harare, Zimbabwe.,TIBA Partnership, NIHR Global Health Research Unit Tackling Infections to Benefit Africa (TIBA), University of Edinburgh, Edinburgh, UK
| | - Margo Chase-Topping
- Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, UK
| | - Lorraine T Pfavayi
- Asthma, Allergy and Immunology Clinic, Twin Palms Medical Centre, Harare, Zimbabwe
| | - Mark E J Woolhouse
- TIBA Partnership, NIHR Global Health Research Unit Tackling Infections to Benefit Africa (TIBA), University of Edinburgh, Edinburgh, UK.,Usher Institute of Population Health Sciences and Informatics and Centre for Immunity, Infection and Evolution, School of Biological Sciences, University of Edinburgh, Edinburgh, UK
| | - Francisca Mutapi
- TIBA Partnership, NIHR Global Health Research Unit Tackling Infections to Benefit Africa (TIBA), University of Edinburgh, Edinburgh, UK.,Institute of Immunology and Infection Research, Centre for Immunity, Infection and Evolution, School of Biological Sciences, Ashworth Laboratories, University of Edinburgh, Edinburgh, UK
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45
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Ribero S, Sciascia S, Borradori L, Lipsker D. The Cutaneous Spectrum of Lupus Erythematosus. Clin Rev Allergy Immunol 2018; 53:291-305. [PMID: 28752372 DOI: 10.1007/s12016-017-8627-2] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Systemic lupus erythematosus is a complex autoimmune disease with a wide spectrum of clinical and immunopathological features. Cutaneous and articular manifestations are the most common signs in patients with systemic lupus erythematosus. We here review the pathogenesis and the new classification of cutaneous lupus erythemathosus with a discussion of the significance of the various cutaneous signs. The lesions are classified according to the level of the cellular infiltrate and tissue damage in the epidermis, dermis, and/or subcutis. Furthermore, cutaneous lesions pointing to the presence of a thrombotic vasculopathy and those due to a distinct inflammatory, neutrophilic-mediated reaction pattern are highlighted. Particular attention will be given in describing the histology of skin manifestation. Treatment options for cutaneous lupus erythemathosus have increased with the introduction of new biological therapies. However, the majority of the patients still benefit from antimalarials, which remain the cornerstone of treatment. The evaluation and management of cutaneous lupus erythemathosus patients depend on the clinical findings and associated symptoms.
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Affiliation(s)
- Simone Ribero
- Department of Medical Sciences, Section of Dermatology, University of Turin, Turin, Italy.
| | - Savino Sciascia
- Center of Research of Immunopathology and Rare Diseases- Department of Clinical and Biological Sciences, University of Turin, San Giovanni Hospital, Turin, Italy
| | - Luca Borradori
- Department of Dermatology, University of Bern, Inselspital, Berne, Switzerland
| | - Dan Lipsker
- Dermatologic Clinic, Faculty of Medicine, University of Strasbourg, Strasbourg, France
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46
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Doerner J, Chalmers SA, Friedman A, Putterman C. Fn14 deficiency protects lupus-prone mice from histological lupus erythematosus-like skin inflammation induced by ultraviolet light. Exp Dermatol 2018; 25:969-976. [PMID: 27305603 DOI: 10.1111/exd.13108] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/01/2016] [Indexed: 12/13/2022]
Abstract
The cytokine TNF-like weak inducer of apoptosis (TWEAK) and its receptor Fn14 are involved in cell survival and cytokine production. The TWEAK/Fn14 pathway plays a role in the pathogenesis of spontaneous cutaneous lesions in the MRL/lpr lupus strain; however, the role of TWEAK/Fn14 in disease induced by ultraviolet B (UVB) irradiation has not been explored. MRL/lpr Fn14 knockout (KO) was compared to MRL/lpr Fn14 wild-type (WT) mice following exposure to UVB. We found that irradiated MRL/lpr KO mice had significantly attenuated cutaneous disease when compared to their WT counterparts. There were also fewer infiltrating immune cells (CD3+ , IBA-1+ and NGAL+ ) in the UVB-exposed skin of MRL/lpr Fn14KO mice, as compared to Fn14WT. Furthermore, we identified several macrophage-derived proinflammatory chemokines with elevated expression in MRL/lpr mice after UV exposure. Depletion of macrophages, using a CSF-1R inhibitor, was found to be protective against the development of skin lesions after UVB exposure. In combination with the phenotype of the MRL/lpr Fn14KO mice, these findings indicate a critical role for Fn14 and recruited macrophages in UVB-triggered cutaneous lupus. Our data strongly suggest that TWEAK/Fn14 signalling is important in the pathogenesis of UVB-induced cutaneous disease manifestations in the MRL/lpr model of lupus and further support this pathway as a possible target for therapeutic intervention.
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Affiliation(s)
- Jessica Doerner
- The Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Samantha A Chalmers
- The Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Adam Friedman
- Department of Dermatology, George Washington University School of Medicine & Health Sciences, Washington, DC, USA
| | - Chaim Putterman
- The Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.,Division of Rheumatology, Albert Einstein College of Medicine, Bronx, NY, USA
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47
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Manikkath S, Venkatta RB, Nair SP, Kumar GN. Verrucous Disseminated Discoid Lupus Erythematosus with Plantar and Oral Lesions in the Absence of Systemic Lupus Erthyematosus. Indian Dermatol Online J 2018; 9:129-131. [PMID: 29644204 PMCID: PMC5885623 DOI: 10.4103/idoj.idoj_125_17] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Affiliation(s)
- Sruthy Manikkath
- Department of Dermatology and Venereology, Government Medical College, Trivandrum, Kerala, India
| | | | - Sukumaran Pradeep Nair
- Department of Dermatology and Venereology, Government Medical College, Trivandrum, Kerala, India
| | - Gopinathan Nanda Kumar
- Department of Dermatology and Venereology, Government Medical College, Trivandrum, Kerala, India
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48
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Yang JY, Cho SY, Kim YC. Cutaneous Lupus Erythematosus Presenting as Localized Grouped Papules Mimicking Herpes Zoster on the Back. Ann Dermatol 2018; 30:731-732. [PMID: 33911519 PMCID: PMC7992465 DOI: 10.5021/ad.2018.30.6.731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Revised: 12/21/2017] [Accepted: 12/31/2017] [Indexed: 11/15/2022] Open
Affiliation(s)
- Ji Young Yang
- Department of Dermatology, Ajou University School of Medicine, Suwon, Korea
| | - Soo Yeon Cho
- Department of Dermatology, Ajou University School of Medicine, Suwon, Korea
| | - You Chan Kim
- Department of Dermatology, Ajou University School of Medicine, Suwon, Korea
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49
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Jurakić Tončić R, Marinovic B, Balić A, Pavičić B, Ljubojević Hadžavdić S, Bradamante M. Bizarre appearance of chronic cutaneous lupus erythematosus of face mimicking factitial dermatitis. J Eur Acad Dermatol Venereol 2017; 32:e215-e216. [PMID: 29224226 DOI: 10.1111/jdv.14747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- R Jurakić Tončić
- University Department of Dermatology and Venereology, Clinical Hospital Center Zagreb and School of Medicine of University in Zagreb, Salata 4, Zagreb, 10000, Croatia
| | - B Marinovic
- University Department of Dermatology and Venereology, Clinical Hospital Center Zagreb and School of Medicine of University in Zagreb, Salata 4, Zagreb, 10000, Croatia
| | - A Balić
- University Department of Dermatology and Venereology, Clinical Hospital Center Zagreb and School of Medicine of University in Zagreb, Salata 4, Zagreb, 10000, Croatia
| | - B Pavičić
- University Department of Dermatology and Venereology, Clinical Hospital Center Zagreb and School of Medicine of University in Zagreb, Salata 4, Zagreb, 10000, Croatia
| | - S Ljubojević Hadžavdić
- University Department of Dermatology and Venereology, Clinical Hospital Center Zagreb and School of Medicine of University in Zagreb, Salata 4, Zagreb, 10000, Croatia
| | - M Bradamante
- University Department of Dermatology and Venereology, Clinical Hospital Center Zagreb and School of Medicine of University in Zagreb, Salata 4, Zagreb, 10000, Croatia
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50
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Taniguchi T, Miyagawa T, Tamaki Z, Nakamura K, Yamashita T, Saigusa R, Takahashi T, Toyama T, Ichimura Y, Yoshizaki A, Tada Y, Sugaya M, Kadono T, Sato S, Asano Y. A possible implication of reduced levels of LIF, LIFR, and gp130 in vasculopathy related to systemic sclerosis. Arch Dermatol Res 2017; 309:833-842. [DOI: 10.1007/s00403-017-1786-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2016] [Revised: 09/10/2017] [Accepted: 10/04/2017] [Indexed: 12/18/2022]
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