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Bishnoi A, Sharma A, Baskaran N, Mehta H, Chatterjee D, Vinay K. Acquired autoinflammatory disorders: a dermatologist's perspective. Clin Exp Dermatol 2025; 50:928-939. [PMID: 39671562 DOI: 10.1093/ced/llae544] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Revised: 11/17/2024] [Accepted: 12/03/2024] [Indexed: 12/15/2024]
Abstract
Autoinflammatory disorders are characterized by a dysregulated and disproportionately heightened response by the innate immune system to PAMPs and DAMPs (pathogen- and damage-associated molecular patterns, respectively), with a crucial role played by neutrophils and macrophages in disease pathogenesis. Autoinflammatory disorders closely resemble connective tissue diseases (CTDs); however, tests for antinuclear antibodies, typically considered a marker of CTDs, are negative in autoinflammatory disorders. Many autoinflammatory disorders are monogenic and arise from inherited genetic mutations, resulting in autoinflammation. This is especially true for disorders presenting in childhood or early adulthood. However, with the relatively recent identification of VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, the recognized genetic spectrum of these disorders has expanded, especially in the adult population, emphasizing that these mutations could either be inherited or acquired later in life. Additionally, many of the acquired autoinflammatory disorders, for example, adult-onset Still disease and Schnitzler syndrome, have a multifactorial pathogenesis and are typically polygenic. Many novel disorders are being described in this category, and the majority of them have prominent cutaneous manifestations - either at onset or during the course of disease - that are particularly important from a diagnostic point of view. In this review, we discuss the cutaneous findings of a few acquired autoinflammatory disorders, with a specific focus on adult-onset Still disease, VEXAS syndrome, Schnitzler syndrome, Kikuchi-Fujimoto disease and haemophagocytic lymphohistiocytosis.
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Affiliation(s)
- Anuradha Bishnoi
- Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Apoorva Sharma
- Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Narayanan Baskaran
- Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Hitaishi Mehta
- Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Debajyoti Chatterjee
- Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Keshavamurthy Vinay
- Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Iwanami K, Hayase T, Masuda Y, Nomura A, Nakamichi Y, Hiraoka E. Persistent Pruritic Linear Streaks of Adult-Onset Still's Disease: Reconsidering the Yamaguchi Criteria. Cureus 2024; 16:e62267. [PMID: 39006577 PMCID: PMC11245378 DOI: 10.7759/cureus.62267] [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: 06/12/2024] [Indexed: 07/16/2024] Open
Abstract
Objective Adult-onset Still's disease (AOSD) is a rare orphan disease, the diagnosis of which remains challenging. This study aimed to identify additional clues for establishing early diagnosis beyond the existing criteria. Methods A retrospective longitudinal cohort study was conducted at two community hospitals in Japan between March 2012 and December 2022. The clinical characteristics and medical histories of patients with AOSD were extracted from the clinical records. The primary outcome was to identify the key manifestations of AOSD for an early diagnosis beyond the existing criteria. Results Twenty-one patients (mean age, 58 years) were included in the study. Fever was the first symptom in 13 out of 21 patients (62%). Six out of 21 patients (29%) presented with a pruritic rash only, while two out of 21 (10%) initially presented with a sore throat. All patients visited more than one medical institution. The median time to reach a correct diagnosis was 41 days (IQR 19-138). Nineteen out of 20 patients (95%) exhibited a pruritic rash, identified as persistent pruritic linear streaks, with a median duration of 21 days (IQR 12-64) before the diagnosis of AOSD as a cutaneous manifestation. Conclusions Persistent pruritic linear streaks were a key feature in the context of an early diagnosis of AOSD, offering an option for reconsidering and revising the existing classification criteria.
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Affiliation(s)
- Keiichi Iwanami
- Department of Rheumatology, Tokyo Bay Urayasu Ichikawa Medical Center, Urayasu, JPN
| | - Takuya Hayase
- Department of Internal Medicine, Tokyo Bay Urayasu Ichikawa Medical Center, Urayasu, JPN
| | - Yohei Masuda
- Department of Internal Medicine, Tokyo Bay Urayasu Ichikawa Medical Center, Urayasu, JPN
| | - Atsushi Nomura
- Department of Rheumatology, Ushiku Aiwa General Hospital, Ushiku, JPN
| | - Yusuke Nakamichi
- Department of Rheumatology, Tokyo Metropolitan Ohtsuka Hospita, Tokyo, JPN
| | - Eiji Hiraoka
- Department of Internal Medicine, Tokyo Bay Urayasu Ichikawa Medical Center, Urayasu, JPN
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Orakwue A, Bray J, Comfere N, Sokumbi O. Neutrophilic Urticarial Dermatosis. Dermatol Clin 2024; 42:219-229. [PMID: 38423683 DOI: 10.1016/j.det.2023.08.009] [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: 03/02/2024]
Abstract
Neutrophilic urticarial dermatosis (NUD) is a rare form of dermatosis that is poorly understood. It was first described by Kieffer and colleagues as an urticarial eruption that is histopathologically characterized by a perivascular and interstitial neutrophilic infiltrate with intense leukocytoclasia and without vasculitis or dermal edema. NUD clinically presents as a chronic or recurrent eruption that consists of nonpruritic macules, papules, or plaques that are pink to reddish and that resolve within 24 hours without residual pigmentation. NUD is often associated with systemic diseases such as Schnitzler syndrome, lupus erythematosus, adult-onset Still's disease, and cryopyrin-associated periodic syndromes.
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Affiliation(s)
- Amarachi Orakwue
- University of Minnesota Medical School, 420 Delaware Street Southeast Suite C607, Minneapolis, MN 55455, USA
| | - Jeremy Bray
- Department of Dermatology, Mayo Clinic, 4500 San Pablo Road S, Jacksonville, FL 32224, USA
| | - Nneka Comfere
- Department of Dermatology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA; Department of Laboratory Medicine & Pathology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
| | - Olayemi Sokumbi
- Department of Dermatology, Mayo Clinic, 4500 San Pablo Road S, Jacksonville, FL 32224, USA; Department of Laboratory Medicine & Pathology, Mayo Clinic, 4500 San Pablo Road S, Jacksonville, FL 32224, USA.
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Tjahjono L, Czaja R, Lalor L, Hasse-Rupp B, Wanat KA. Persistent papules and plaques in systemic juvenile idiopathic arthritis. Pediatr Dermatol 2022; 39:616-618. [PMID: 35560434 DOI: 10.1111/pde.15029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 04/23/2022] [Indexed: 11/30/2022]
Abstract
A 6-year-old girl presented with nightly fever, persistent joint pain of the knees, ankles, lower back, and hip. Her skin lesions were evanescent salmon-colored patches along with persistent pruritic light to dark pink papules and plaques on her face, post-auricular scalp, trunk, thigh, and bilateral upper extremities. Skin biopsy supported the diagnosis of fixed papules and plaques of systemic juvenile idiopathic arthritis (sJIA). We report this case to highlight diagnostic features of this exceedingly rare cutaneous presentation of sJIA presenting with typical cutaneous salmon-colored evanescent eruptions.
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Affiliation(s)
- Leonardo Tjahjono
- Department of Dermatology, Medical College of Wisconsin, Wauwatosa, Wisconsin, USA
| | - Rebecca Czaja
- Department of Pathology, Medical College of Wisconsin, Wauwatosa, Wisconsin, USA
| | - Leah Lalor
- Department of Dermatology, Medical College of Wisconsin, Wauwatosa, Wisconsin, USA
| | - Brenda Hasse-Rupp
- Department of Dermatology, Medical College of Wisconsin, Wauwatosa, Wisconsin, USA
| | - Karolyn A Wanat
- Department of Dermatology, Medical College of Wisconsin, Wauwatosa, Wisconsin, USA.,Department of Pathology, Medical College of Wisconsin, Wauwatosa, Wisconsin, USA
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Patidar A, Parikh PM, Balai M, Mittal A. Flagellate Rash in Adult-onset Still's Disease. Indian Dermatol Online J 2021; 12:159-161. [PMID: 33768042 PMCID: PMC7982050 DOI: 10.4103/idoj.idoj_178_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Revised: 04/11/2020] [Accepted: 05/21/2020] [Indexed: 11/06/2022] Open
Affiliation(s)
- Abhilasha Patidar
- Department of Dermatology, Venereology and Leprology, R.N.T. Medical College, Udaipur, Rajasthan, India
| | - Prashant M Parikh
- Senior Consultant Pathologist, Neuberg Supratech Reference Laboratories, Ahmedabad, Gujarat, India
| | - Manisha Balai
- Department of Dermatology, Venereology and Leprology, R.N.T. Medical College, Udaipur, Rajasthan, India
| | - Asit Mittal
- Department of Dermatology, Venereology and Leprology, R.N.T. Medical College, Udaipur, Rajasthan, India
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Rao S, Li Q, Wu H, Zhao M, Wang A, Zhang G, Li J, Lu L, Shi W, Lu Q. Juxtaposition of IL-1β and IFN-γ expression and apoptosis of keratinocytes in adult-onset Still's disease. Expert Rev Clin Immunol 2019; 15:1341-1350. [PMID: 31661988 DOI: 10.1080/1744666x.2020.1685876] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Backgroud: Recently, atypical persistent skin eruptions (APSEs) have been documented as a new manifestation of adult-onset Still's disease (AOSD), with a unique pathological feature of necrotic keratinocytes in the upper third of the epidermis, but the mechanism has not been elucidated. The aim of this study was to explore the potential mechanism of the unique pathological phenomenon of APSEs.Methods: Clinical and pathological data from 26 AOSD patients with APSEs and 6 with evanescent skin eruptions (ESEs) were reviewed. Fourteen APSE biopsies and 6 ESE biopsies were selected for multi-spectrum immunohistochemistry with 5 disease controls and 5 healthy controls.Results: The unique pathological manifestation was present in all APSE patients but was hardly found in ESE patients. There were more CD4 + T-cells infiltrated in the dermis of APSEs than in the dermis of ESEs. IL-1β and IFN-γ were specifically expressed in the upper third of the epidermis and were juxtaposed to the loci of the necrotic keratinocytes.Conclusion: Our findings showed important cellular and molecular derangements related to the APSE-specific pathological phenomena and helped to understand the pathogenesis of dyskeratosis in the epidermis. The findings could also pave a way to explore an effective intervention to this potentially life-threatening disorder.
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Affiliation(s)
- Shijia Rao
- Department of Dermatology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, PR China
| | - Qianwen Li
- Department of Dermatology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, PR China
| | - Haijing Wu
- Department of Dermatology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, PR China
| | - Ming Zhao
- Department of Dermatology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, PR China
| | - Alun Wang
- Department of Pathology, Tulane University School of Medicine, New Orleans, LA, USA
| | - Guiying Zhang
- Department of Dermatology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, PR China
| | - Ji Li
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, PR China
| | - Lixia Lu
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, PR China
| | - Wei Shi
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, PR China
| | - Qianjin Lu
- Department of Dermatology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, PR China
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Damevska K, França K, Nikolovska S, Gucev F. Adult-onset Still's disease as a cutaneous marker of systemic disease. Clin Dermatol 2019; 37:668-674. [PMID: 31864446 DOI: 10.1016/j.clindermatol.2019.07.034] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Adult-onset Still's disease (AOSD) is a rare, systemic, inflammatory disorder characterized by spiking fevers, an evanescent eruption, arthritis, and multiorgan involvement. The disease has been recently classified as a polygenic autoinflammatory disorder at the "crossroads" of autoinflammatory and autoimmune diseases. The highly characteristic salmon-colored eruption is a cutaneous manifestation of a generalized inflammatory reaction and an important diagnostic criterion. In addition to the evanescent eruption, there are atypical persistent papules and plaques in many patients with AOSD. Emerging data suggest that AOSD with this typical evanescent eruption has a different clinicopathologic presentation and clinical course than AODS with atypical cutaneous manifestations. It appears that there are two subtypes of AOSD with different immunologic profiles, including (1) a systemic disease with high fever, organ involvement, and elevated levels of ferritin, and (2) a chronic disease course with arthritis as the predominant finding. These observations provide novel insight into the disease pathogenesis, suggesting that the underlying mechanisms might differ between these two forms, partially explaining the reported differences in drug response. Recent advances in the understanding of AOSD are summarized with a focus on the spectrum of cutaneous manifestations and its relationship to systemic inflammation.
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Affiliation(s)
- Katerina Damevska
- University Clinic of Dermatology, Ss Cyril and Methodius University, Skopje, Macedonia.
| | - Katlein França
- Department of Dermatology and Cutaneous Surgery, Department of Psychiatry and Behavioral Sciences, Institute for Bioethics and Health Policy, University of Miami Miller School of Medicine, Miami, Florida, USA
| | - Suzana Nikolovska
- University Clinic of Dermatology, Ss Cyril and Methodius University, Skopje, Macedonia
| | - Filip Gucev
- Univeristy Clinic of Rheumatology, Ss Cyriland Methodius University, Skopje, Macedonia
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Abstract
Flagellate erythema is a distinctive eruption characterized by "whip-like" linear or curvilinear streaks and plaques, occurring mainly on the trunk. It has classically been described in 2 disparate clinical settings: chemotherapy with bleomycin and ingestion of mushrooms (most commonly Shiitake mushrooms). Most of the literature comprises single case reports, often with minimal histological description of rather nonspecific features. We describe in detail the histological features of 3 cases of flagellate erythema (2 related to bleomycin therapy and one related to ingestion of mushrooms) and review the findings described in the literature to define the spectrum of histological changes encountered in this eruption. Our 3 cases showed mild epidermal changes, with spongiosis and variable interface inflammation. All 3 showed a relatively prominent dermal lymphohistiocytic infiltrate, with features suggestive of a lymphocytic vasculopathy extending to at least the mid-reticular dermis. Eosinophils were a prominent component of the inflammatory infiltrate in 2 cases. Our review of the literature identified a total of 45 publications, representing reports of 46 patients, containing histological information. As well as bleomycin- and mushroom-related cases, similar eruptions have been reported in the context of connective tissue disease and other drugs. Although cases related to connective tissue disease show features of the underlying condition, cases secondary to drugs or mushrooms predominantly show features compatible with common patterns of exanthematous/morbilliform drug reaction. In particular, subtle spongiosis and/or interface dermatitis combined with a dermal lymphocytic infiltrate that includes increased numbers of eosinophils is a common finding. Features of a lymphocytic vasculopathy may be seen in a subset of these cases.
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9
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Nassereddine H, Fite C, Kottler D, Descamps V, Couvelard A, Marot L, Deschamps L. An atypical persistent eruption of adult-onset Still's disease with neutrophilic urticarial dermatosis-like dermal features: A case report and review of the literature. J Cutan Pathol 2018; 45:793-799. [PMID: 29992610 DOI: 10.1111/cup.13320] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2018] [Revised: 07/01/2018] [Accepted: 07/06/2018] [Indexed: 11/28/2022]
Affiliation(s)
- Hussein Nassereddine
- AP-HP, Bichat-Hospital, Department of Pathology, Paris Descartes University, Paris, France
| | - Charlotte Fite
- AP-HP, Bichat-Hospital, Department of Dermatology, Paris Diderot University, Paris, France
| | - Diane Kottler
- AP-HP, Bichat-Hospital, Department of Dermatology, Paris Diderot University, Paris, France
| | - Vincent Descamps
- AP-HP, Bichat-Hospital, Department of Dermatology, Paris Diderot University, Paris, France
| | - Anne Couvelard
- AP-HP, Bichat-Hospital, Department of Pathology, Paris Diderot University, Paris, France
| | - Liliane Marot
- Department of Pathology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Lydia Deschamps
- AP-HP, Bichat-Hospital, Department of Pathology, Paris Diderot University, Paris, France
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10
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Narváez Garcia FJ, Pascual M, López de Recalde M, Juarez P, Morales-Ivorra I, Notario J, Jucglà A, Nolla JM. Adult-onset Still's disease with atypical cutaneous manifestations. Medicine (Baltimore) 2017; 96:e6318. [PMID: 28296747 PMCID: PMC5369902 DOI: 10.1097/md.0000000000006318] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
The diagnosis of adult-onset Still's disease (AOSD) can be very difficult. There are no specific tests available, and diagnosis is usually based on a symptom complex and the well-described typical evanescent rash seen in the majority of patients. However, in recent years, other atypical cutaneous manifestations of AOSD have been reported. These atypical skin eruptions often present in addition to the typical evanescent rash but may also be the only skin manifestation, resulting in delayed diagnosis because of under-recognition.In this study, we present 3 new cases of AOSD with atypical cutaneous manifestations diagnosed during a 30-year period in our department and review 78 additional cases previously reported (PubMed 1990-2016). These 81 patients form the basis of the present analysis.The overall prevalence of atypical cutaneous manifestations in our AOSD population was 14%. These manifestations may appear at any time over the course of the disease, and usually occur in patients who have persistent and severe disease, with a considerable frequency of clinical complications (23%), including serositis, myopericarditis, lung involvement, abdominal pain, neurologic involvement, and reactive hemophagocytic syndrome.The most representative and frequent lesion among the nonclassical skin rashes is the development of persistent pruritic papules and/or plaques. Interestingly, these lesions show a distinctive histological pattern. Other, less frequently observed lesions include urticaria and urticaria-like eruptions, generalized or widespread non-pruritic persistent erythema, vesiculopustular eruptions, a widespread peau d'orange appearance of the skin, and edema of the eyelids mimicking dermatomyositis without any accompanying skin lesion.The great majority of these patients required medium or high doses of glucocorticoids (including intravenous methylprednisolone pulse therapy in some cases) and, in nearly 40%, a more potent or maintenance immunotherapy with immunosuppressant drugs and/or biologic agents (mainly anakinra or tocilizumab) to control or manage symptoms because of a polycyclic or chronic course. The development of atypical cutaneous manifestations seems to be associated with a potentially worse prognosis, with a mortality rate reaching 8% primarily because of infectious complications related to immunosuppressive therapy.In conclusion, the appearance of atypical cutaneous manifestations is not uncommon in AOSD. Recognition of this clinical variant is crucial for the early diagnosis of AOSD, as it might imply persistent disease activity and the need for more aggressive treatment.
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Affiliation(s)
| | | | | | | | | | - Jaime Notario
- Department of Dermatology, Hospital Universitario de Bellvitge-IDIBELL, Barcelona, Spain
| | - Anna Jucglà
- Department of Dermatology, Hospital Universitario de Bellvitge-IDIBELL, Barcelona, Spain
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Ruscitti P, Cipriani P, Ciccia F, Di Benedetto P, Liakouli V, Berardicurti O, Carubbi F, Guggino G, Di Bartolomeo S, Triolo G, Giacomelli R. H-ferritin and CD68(+) /H-ferritin(+) monocytes/macrophages are increased in the skin of adult-onset Still's disease patients and correlate with the multi-visceral involvement of the disease. Clin Exp Immunol 2016; 186:30-8. [PMID: 27317930 DOI: 10.1111/cei.12826] [Citation(s) in RCA: 38] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/07/2016] [Indexed: 12/28/2022] Open
Abstract
Adult-onset Still's disease (AOSD) patients may show an evanescent salmon-pink erythema appearing during febrile attacks and reducing without fever. Some patients may experience this eruption for many weeks. During AOSD, exceptionally high serum levels of ferritin may be observed; it is an iron storage protein composed of 24 subunits, heavy (H) subunits and light (L) subunits. The ferritin enriched in L subunits (L-ferritin) and the ferritin enriched in H subunits (H-ferritin) may be observed in different tissues. In this work, we aimed to investigate the skin expression of both H-and L-ferritin and the number of macrophages expressing these molecules from AOSD patients with persistent cutaneous lesions. We observed an increased expression of H-ferritin in the skin, associated with an infiltrate in the biopsies obtained from persistent cutaneous lesions of AOSD patients. Furthermore, a positive correlation between H-ferritin skin levels as well as the number of CD68(+) /H-ferritin(+) cells and the multi-visceral involvement of the disease was observed. Our data showed an increased expression of H-ferritin in the skin of AOSD patients, associated with a strong infiltrate of CD68(+) /H-ferritin(+) cells. Furthermore, a correlation between the levels of H-ferritin as well as of the number of CD68(+) /H-ferritin(+) cells and the multi-visceral involvement of the disease was observed.
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Affiliation(s)
- P Ruscitti
- Division of Rheumatology, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, Italy
| | - P Cipriani
- Division of Rheumatology, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, Italy
| | - F Ciccia
- Division of Rheumatology, Department of Internal Medicine, University of Palermo, Palermo, Italy
| | - P Di Benedetto
- Division of Rheumatology, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, Italy
| | - V Liakouli
- Division of Rheumatology, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, Italy
| | - O Berardicurti
- Division of Rheumatology, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, Italy
| | - F Carubbi
- Division of Rheumatology, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, Italy
| | - G Guggino
- Division of Rheumatology, Department of Internal Medicine, University of Palermo, Palermo, Italy
| | - S Di Bartolomeo
- Division of Rheumatology, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, Italy
| | - G Triolo
- Division of Rheumatology, Department of Internal Medicine, University of Palermo, Palermo, Italy
| | - R Giacomelli
- Division of Rheumatology, Department of Biotechnological and Applied Clinical Science, School of Medicine, University of L'Aquila, L'Aquila, Italy
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12
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Cozzi A, Papagrigoraki A, Biasi D, Colato C, Girolomoni G. Cutaneous manifestations of adult-onset Still's disease: a case report and review of literature. Clin Rheumatol 2016; 35:1377-82. [PMID: 24737284 DOI: 10.1007/s10067-014-2614-2] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2014] [Revised: 04/01/2014] [Accepted: 04/02/2014] [Indexed: 02/07/2023]
Abstract
Adult onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology and pathogenesis characterized by high spiking fever, arthralgia or arthritis, sore throat, lymphadenopathy, hepatosplenomegaly, serositis, and transient cutaneous manifestations. Although more common in children, cases are seen also in adults. Cutaneous involvement is common and may be suggestive for the diagnosis. A case of AOSD in a 35-year-old man is reported here, presenting with urticarial maculopapular rash of trunk, high spiking fever, acute respiratory distress syndrome, and myopericarditis. Skin biopsy showed interstitial and perivascular mature CD15(+) neutrophils. A comprehensive review of literature showed that cutaneous involvement occurs in about 80 % of patients, with various clinical presentations. The most common skin manifestation is an evanescent salmon pink or erythematous maculopapular exanthema, predominantly on the trunk and proximal limbs, with rare involvement of face and distal limbs. Less common manifestations include persistent erythematous plaques and pustular lesions. A constant histopathologic finding is the presence of interstitial dermal neutrophils aligned between the collagen bundles. This pattern may provide an easy accessible clue for the definitive diagnosis of AOSD and exclude other diagnosis such as drug eruptions or infectious diseases.
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Affiliation(s)
- Alessandra Cozzi
- Department of Medicine, Section of Dermatology and Venereology, University of Verona, Piazzale A. Stefani 1, 37126, Verona, Italy
| | - Anastasia Papagrigoraki
- Department of Medicine, Section of Dermatology and Venereology, University of Verona, Piazzale A. Stefani 1, 37126, Verona, Italy
| | - Domenico Biasi
- Department of Medicine, Section of Rheumatology, University of Verona, Piazzale A. Stefani 1, 37126, Verona, Italy
| | - Chiara Colato
- Department of Pathology and Diagnostics, Section of Pathology, University of Verona, Piazzale A. Stefani 1, 37126, Verona, Italy
| | - Giampiero Girolomoni
- Department of Medicine, Section of Dermatology and Venereology, University of Verona, Piazzale A. Stefani 1, 37126, Verona, Italy.
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13
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Michailidou D, Shin J, Forde I, Gopalratnam K, Cohen P, DeGirolamo A. Typical evanescent and atypical persistent polymorphic cutaneous rash in an adult Brazilian with Still's disease: a case report and review of the literature. AUTO- IMMUNITY HIGHLIGHTS 2015; 6:39-46. [PMID: 26423534 PMCID: PMC4633415 DOI: 10.1007/s13317-015-0071-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/18/2015] [Accepted: 09/11/2015] [Indexed: 12/18/2022]
Abstract
Adult onset Still's disease (AOSD) is a systemic auto-inflammatory condition of unknown etiology, characterized by high fever, an evanescent, salmon-pink maculopapular skin rash, arthralgia or arthritis and leukocytosis. AOSD can also present with atypical cutaneous manifestations, such as persistent pruritic coalescent papules or plaques and linear lesions that have highly distinctive pathological features and are usually associated with severe disease. Herein, we present a 31-year-old Brazilian man with both typical Still's rash and atypical persistent polymorphic cutaneous manifestations associated with severe systemic inflammatory response syndrome. Eosinophils that are consistently lacking in the AOSD-associated skin lesions were evident in the skin biopsy of the persistent atypical cutaneous manifestations and were either drug-related or AOSD-associated.
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Affiliation(s)
- Despina Michailidou
- Department of Internal Medicine, Bridgeport Hospital, Yale-New Haven Health System, Bridgeport, CT, USA.
| | - Junghee Shin
- Department of Internal Medicine, Bridgeport Hospital, Yale-New Haven Health System, Bridgeport, CT, USA
| | - Inga Forde
- Section of Pulmonary, Critical Care and Sleep Medicine, Bridgeport Hospital, Yale-New Haven Health System, Bridgeport, CT, USA
| | - Kavitha Gopalratnam
- Department of Internal Medicine, Bridgeport Hospital, Yale-New Haven Health System, Bridgeport, CT, USA
| | - Paul Cohen
- Department of Pathology, Bridgeport Hospital, Yale University School of Medicine, New Haven, CT, USA
| | - Angela DeGirolamo
- Department of Internal Medicine, Bridgeport Hospital, Yale-New Haven Health System, Bridgeport, CT, USA
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Trastuzumab-Associated Flagellate Erythema: Report in a Woman with Metastatic Breast Cancer and Review of Antineoplastic Therapy-Induced Flagellate Dermatoses. Dermatol Ther (Heidelb) 2015; 5:253-264. [PMID: 26506993 PMCID: PMC4674452 DOI: 10.1007/s13555-015-0085-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2015] [Indexed: 12/18/2022] Open
Abstract
Introduction Flagellate erythema presents as erythematous, individual and intermingled, linear streaks in a whiplash-like pattern. Several conditions, including antineoplastic agents, have been associated with flagellate erythema. A woman with metastatic breast cancer who developed flagellate erythema after receiving trastuzumab is described and the features of flagellate erythema associated with other antineoplastic agents are reviewed. Methods PubMed was used to search the following terms, separately and in combination: agent, antineoplastic, bendamustine, bleomycin, breast, cancer, chemotherapy, dermatitis, dermatosis, docetaxel, erythema, flagellate, Herceptin, pigmentation, peplomycin, therapy, and trastuzumab. All papers were reviewed and relevant manuscripts, along with their reference citations, were evaluated. Results The woman’s pruritus and skin lesions promptly resolved after treatment with corticosteroids (oral and topical) and antihistamines (oral); premedication with dexamethasone prior to each subsequent trastuzumab treatment prevented recurrence of flagellate erythema. Chemotherapy-induced flagellate erythema was initially described in oncology patients who received bleomycin. In addition to trastuzumab, other antineoplastic agents that have been associated with the development of flagellate erythema include bendamustine, docetaxel, and peplomycin. Conclusion Cutaneous adverse events to trastuzumab are uncommon. However, flagellate erythema should be added to the potential side effects of trastuzumab. In addition, trastuzumab should be added to the list of antineoplastic agents that may be associated with flagellate erythema. Electronic supplementary material The online version of this article (doi:10.1007/s13555-015-0085-2) contains supplementary material, which is available to authorized users.
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Sun NZ, Brezinski EA, Berliner J, Haemel A, Connolly MK, Gensler L, McCalmont TH, Shinkai K. Updates in adult-onset Still disease: Atypical cutaneous manifestations and associations with delayed malignancy. J Am Acad Dermatol 2015; 73:294-303. [PMID: 26054431 DOI: 10.1016/j.jaad.2015.04.063] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Revised: 04/23/2015] [Accepted: 04/30/2015] [Indexed: 10/23/2022]
Abstract
Adult-onset Still disease (AOSD) is a systemic inflammatory disorder that is clinically characterized by a heterogeneous constellation of symptoms and signs. Though an evanescent eruption is the classic cutaneous finding, recent literature has highlighted atypical rashes associated with Still disease. A second emerging concept in presentations of AOSD is its association with malignancy. This review focuses on these concepts: the clinical spectrum of atypical skin manifestations and AOSD as a paraneoplastic phenomenon. PubMed-MEDLINE was screened for peer-reviewed articles describing atypical presentations of AOSD and cases associated with malignancy. Erythematous, brown or violaceous, persistent papules and plaques were the most common cutaneous finding (28/30 [93%]). Linear configurations were also rarely described. Of these patients, 81% concurrently had the typical evanescent skin eruption. There were 31 patients with associated malignancies, most commonly breast cancer and lymphoma. The diagnosis of malignancy did not precede or immediately follow a clinical presentation otherwise consistent with AOSD in a considerable subset of patients (42%). Understanding the cutaneous spectrum of AOSD and heightened awareness for its delayed association with malignancy may lead to improved recognition of cutaneous variants and reinforce the need for diagnostic evaluation and long-term follow-up for malignancy in patients with this clinical presentation.
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Affiliation(s)
- Natalie Z Sun
- Department of Dermatology, University of California San Francisco, San Francisco, California.
| | - Elizabeth A Brezinski
- Department of Internal Medicine, California Pacific Medical Center, San Francisco, California
| | - Jacqueline Berliner
- Department of Dermatology, University of California San Francisco, San Francisco, California
| | - Anna Haemel
- Department of Dermatology, University of California San Francisco, San Francisco, California
| | - M Kari Connolly
- Department of Dermatology, University of California San Francisco, San Francisco, California
| | - Lianne Gensler
- Department of Rheumatology, University of California San Francisco, San Francisco, California
| | - Timothy H McCalmont
- Department of Dermatology, University of California San Francisco, San Francisco, California; Department of Pathology, University of California San Francisco, San Francisco, California
| | - Kanade Shinkai
- Department of Dermatology, University of California San Francisco, San Francisco, California
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16
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Yun D, Stein SL. Review of the cutaneous manifestations of autoimmune connective tissue diseases in pediatric patients. World J Dermatol 2015; 4:80-94. [DOI: 10.5314/wjd.v4.i2.80] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2014] [Revised: 02/25/2015] [Accepted: 04/07/2015] [Indexed: 02/06/2023] Open
Abstract
Autoimmune connective tissue diseases are chronic inflammatory disorders associated with complex genetic and environmental interplay resulting in a variety of cutaneous and systemic manifestations. Pediatric onset of these disorders carries a unique diagnostic pressure for the clinician due to the potential years of disease burden and complications. Mortality and morbidity from these disorders has fallen dramatically over the past fifty years due to increasing awareness of these disease sequelae and utilization of systemic treatment modalities when necessary. This review highlights the clinical features that are unique to pediatric presentations of lupus erythematosus, juvenile idiopathic arthritis, juvenile dermatomyositis, juvenile onset systemic sclerosis and morphea. Each of these disorders has a distinct appearance corresponding to a particular cutaneous and systemic clinical course and prognosis. Awareness of the associated potential systemic complications can also alert the clinician to make astute management decisions when confronted with a probable rheumatologic case. Cutaneous symptoms may predate onset of systemic symptoms and by keeping the rheumatologic differential diagnoses in mind, the dermatologist can play a key role in potentially offsetting autoimmune disease burden in children.
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17
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Kim HA, Kwon JE, Yim H, Suh CH, Jung JY, Han JH. The pathologic findings of skin, lymph node, liver, and bone marrow in patients with adult-onset still disease: a comprehensive analysis of 40 cases. Medicine (Baltimore) 2015; 94:e787. [PMID: 25929927 PMCID: PMC4603035 DOI: 10.1097/md.0000000000000787] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Adult-onset Still disease (AOSD) is characterized by fever, skin rash, and lymphadenopathy with leukocytosis and anemia as common laboratory findings. We investigated the characteristic pathologic findings of skin, lymph node, liver, and bone marrow to assist in proper diagnosis of AOSD.Forty AOSD patients were included in the study. The skin (26 patients), lymph node (8 patients), liver (8 patients), or bone marrow biopsies (22 patients) between 1998 and 2013 were retrospectively analyzed. AOSD patients were diagnosed according to the Yamaguchi criteria after excluding common infections, hematological and autoimmune diseases. Immunohistochemistry, immunofluorescence, and Epstein-Barr virus-encoded RNA (EBER) in situ hybridization were performed.Most skin biopsies revealed mild lymphocytic or histiocytic infiltration in the upper dermis. Nuclear debris was frequently found in the dermis in 14 cases (53.8%). More than half of the cases (n = 14, 53.8%) showed interstitial mucin deposition. Some cases showed interface dermatitis with keratinocyte necrosis or basal vacuolization (n = 10; 38.5%). The lymph node biopsies showed a paracortical or diffuse hyperplasia pattern with immunoblastic and vascular proliferation. The liver biopsies showed sparse portal and sinusoidal inflammatory cell infiltration. All cases showed various degrees of Kupffer cell hyperplasia. The cellularity of bone marrow varied from 20% to 80%. Myeloid cell hyperplasia was found in 14 out of the 22 cases (63.6%). On immunohistochemistry, the number of CD8-positive lymphocytes was greater than that of CD4-positive lymphocytes in the skin, liver, and bone marrow, but the number of CD4-positive lymphocytes was greater than that of CD8-positive lymphocytes in the lymph nodes.The relatively specific findings with respect to the cutaneous manifestation of AOSD were mild inflammatory cell infiltration in the upper dermis, basal vacuolization, keratinocyte necrosis, presence of karyorrhexis, and mucin in the dermis. In all cases, pathologic findings in the lymph nodes included paracortical hyperplasia with vascular and immunoblastic proliferation. Skin and lymph node pathology in addition to clinical findings can aid in the diagnosis of AOSD.
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Affiliation(s)
- Hyoun-Ah Kim
- From the Department of Rheumatology (H-AK, C-HS, J-YJ); and Department of Pathology (JEK, HY, JHH), Ajou University School of Medicine, Suwon, Korea
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Homayounfar G, Zimarowski MJ, Burgin S. A woman with night sweats, arthritis, and two distinct eruptions. Adult-onset Still’s disease (AOSD). Int J Dermatol 2014; 54:865-7. [PMID: 25521498 DOI: 10.1111/ijd.12742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2014] [Accepted: 04/19/2014] [Indexed: 11/29/2022]
Affiliation(s)
| | - Mary J Zimarowski
- Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Susan Burgin
- Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USA
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19
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Kavusi S, Paravar T, Hasteh F, Lee R. Atypical eruption but still Still's: case report and review of the literature. Int J Dermatol 2014; 54:e154-9. [DOI: 10.1111/ijd.12608] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Suzan Kavusi
- Department of Pathology; University of California; San Diego CA USA
| | - Taraneh Paravar
- Department of Dermatology; University of California; San Diego CA USA
| | - Farnaz Hasteh
- Department of Pathology; University of California; San Diego CA USA
| | - Robert Lee
- Department of Dermatology; University of California; San Diego CA USA
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20
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Yoshifuku A, Kawai K, Kanekura T. Adult-onset Still disease with peculiar persistent plaques and papules. Clin Exp Dermatol 2014; 39:503-5. [PMID: 24773396 DOI: 10.1111/ced.12335] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/13/2013] [Indexed: 11/29/2022]
Abstract
Adult-onset Still disease (AOSD) is a systemic inflammatory disorder characterized clinically by high spiking fever, polyarthralgia/arthritis, a salmon-pink evanescent rash, predominantly neutrophilic leucocytosis, lymphadenopathy, liver dysfunction, and splenomegaly. Recently, a nonclassic, nonevanescent skin rash has been reported. We report a 27-year-old woman with AOSD showing persistent pruritic papular lesions. Histologically, dyskeratotic keratinocytes were seen in the upper epidermis. We describe this case in detail and review the previous literature. Nonclassic pruritic eruptions with characteristic dyskeratotic keratinocytes might provide an important clue for the diagnosis of AOSD.
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Affiliation(s)
- A Yoshifuku
- Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Japan
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21
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Kikuchi N, Satoh M, Ohtsuka M, Yamamoto T. Persistent pruritic papules and plaques associated with adult-onset Still's disease: report of six cases. J Dermatol 2014; 41:407-10. [PMID: 24628100 DOI: 10.1111/1346-8138.12426] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2013] [Accepted: 01/09/2014] [Indexed: 12/29/2022]
Abstract
Typical skin rash, which appears and disappears along with respective rise and fall of fever, is well-known, and included as one of the major criteria of adult-onset Still's disease (AOSD) (Yamaguchi's criteria). In addition, various skin lesions are occasionally observed in association with AOSD. Persistent pruritic eruptions present with some clinical features, such as urticarial erythema, flagellate erythema, erythematous, slightly scaly or crusted papules, and/or plaques on the trunk and extremities. These lesions show unique histological features such as dyskeratosis with a peculiar, distinctive distribution in the upper epidermis and cornified layers with focal hyperkeratosis. We describe herein six cases of AOSD, which presented with skin lesions of persistent pruritic papules and plaques. All six cases were female, and three of them were elderly women. The patients presented with linear erythematous streaks, scaly erythema, keratotic papules, infiltrative plaques and irregular coalesced erythemas. By contrast, histological features were characteristic, and dyskeratotic cells were found in the horny layers as well as in the upper layers of the epidermis. Persistent pruritic eruption is an important cutaneous sign for the diagnosis of AOSD.
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Affiliation(s)
- Nobuyuki Kikuchi
- Department of Dermatology, Fukushima Medical University, Fukushima, Japan
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22
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Sarkar RN, Bhattacharya R, Bhattacharyya K, Paul R, Mullick OS. Adult onset Still's disease with persistent skin lesions complicated by secondary hemophagocytic lymphohistiocytosis. Int J Rheum Dis 2013; 17:118-21. [PMID: 24119099 DOI: 10.1111/1756-185x.12170] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Rathindra N Sarkar
- Department of Medicine, Rheumatology Division, Medical College, Kolkata, India
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23
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NAGAI Y, HASEGAWA M, OKADA E, HATTORI T, TAGO O, ISHIKAWA O. Clinical follow-up study of adult-onset Still’s disease. J Dermatol 2012; 39:898-901. [DOI: 10.1111/j.1346-8138.2012.01600.x] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
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Lee JYY, Hsu CK, Liu MF, Chao SC. Evanescent and persistent pruritic eruptions of adult-onset still disease: a clinical and pathologic study of 36 patients. Semin Arthritis Rheum 2012; 42:317-26. [PMID: 22717204 DOI: 10.1016/j.semarthrit.2012.05.003] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2012] [Revised: 05/03/2012] [Accepted: 05/10/2012] [Indexed: 01/04/2023]
Abstract
OBJECTIVE Persistent pruritic eruptions (PPE) are common among our patients with adult-onset Still disease (AOSD). We aimed to characterize the clinicopathologic features of the AOSD-associated evanescent and persistent rashes. METHODS We reviewed the clinicopathologic features of the skin lesions from all AOSD cases diagnosed in our hospital during 1988 to 2009. The diagnoses were based on Yamaguchi criteria for AOSD. RESULTS Altogether, there were 36 patients (6 men and 30 women) with age of onset ranging from 17 to 67 years (average 35.7 years). Evanescent rash was recorded in 31 patients (86%) and PPEs in 28 (78%). PPEs usually appeared at the disease onset and manifested as widespread, pruritic, erythematous urticarial or violaceous to brownish flat-topped (lichenoid) papules and plaques over the trunk, neck, face, and extensor sides of the extremities. PPEs were classified clinically as urticarial papules (n = 21), lichenoid papules (n = 18), prominent linear and dermographism-like (n = 11), dermatomyositis-like (n = 7), prurigo pigmentosa-like (n = 4), and lichen amyloidosis-like (n = 2). The clinical activity score was 5.78 ± 1.11 (range 4 to 8) for the series and 6.57 ± 0.98 and 5.57 ± 1.07, respectively, for the groups with and without dermatomyositis-like PPE (P = 0.0314). Five patients died, 3 of them with dermatomyositis-like PPE. Histopathologically, the evanescent rash (8 specimens) showed a superficial perivascular infiltrate of lymphocytes and neutrophils, whereas the PPEs (32 specimens) revealed solitary or cluster necrotic keratinocytes in the superficial epidermis with infiltration of lymphocytes and neutrophils in the upper and mid dermis. CONCLUSIONS PPEs were very common among our patients with AOSD. Recognition of the characteristic clinical and pathologic features of PPE can facilitate diagnosis of AOSD. Therefore, biopsy of atypical eruptions in AOSD patients is recommended because it is likely that the highly distinctive histopathologic features will allow these eruptions to be readily classified.
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Affiliation(s)
- Julia Yu-Yun Lee
- Department of Dermatology, National Cheng Kung University, College of Medicine and Hospital, Tainan, Taiwan.
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OHASHI M, MORIYA C, KANOH H, KINOMURA Y, TERAKURA Y, KASAHARA S, HAMAGUCHI Y, FUJIMOTO M, SEISHIMA M. Adult-onset Still’s disease with dermatomyositis-like eruption. J Dermatol 2012; 39:958-60. [DOI: 10.1111/j.1346-8138.2012.01549.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Yamamoto T. Cutaneous manifestations associated with adult-onset Still's disease: important diagnostic values. Rheumatol Int 2011; 32:2233-7. [PMID: 22198666 DOI: 10.1007/s00296-011-2330-z] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2011] [Accepted: 12/10/2011] [Indexed: 11/24/2022]
Abstract
Adult-onset Still's disease (AOSD) is a systemic inflammatory condition, characterized by a high spiking fever, leukocytosis with neutrophilia, arthralgia, and skin rash. Typical skin rash is an evanescent, salmon-pink erythema predominantly involving extremities, which is included as one of the diagnostic criteria; however, recent findings show that not only typical evanescent rash but also various skin lesions are associated with AOSD. The representative characteristic skin lesion among the non-classical skin rash is called persistent pruritic papules and plaques, which presents erythematous, slightly scaly papules with linear configuration on the trunk. Interestingly, persistent pruritic papules and plaques show unique histological features such as peculiar, distinctive distribution of dyskeratotic keratinocytes in the cornified layers as well as in the epidermis. Other non-classical skin lesions include urticaria. Current insights suggest that several inflammatory cytokines such as interleukin-1 (IL-1), IL-6, IL-18, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) play a pathogenic role in AOSD. In particular, IL-18 is suggested to play a crucial role in activating macrophages, favoring Th1 type cytokine production. IL-18 induces IFN-γ, IL-17, and TNF-α, which may play an important pathogenic role in AOSD. It is important to recognize the common and/or uncommon skin conditions of AOSD for early correct diagnosis. In this review, various skin lesions are introduced, and the complication with histiocytic necrotizing lymphadenitis (Kikuchi disease) is further discussed.
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Affiliation(s)
- Toshiyuki Yamamoto
- Department of Dermatology, Fukushima Medical University, Hikarigaoka 1, Fukushima 960-1295, Japan.
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27
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28
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Criado PR, de Carvalho JF, Ayabe LA, Brandt HRC, Romiti R, Maruta CW. Urticaria and dermographism in patients with adult-onset Still's disease. Rheumatol Int 2011; 32:2551-5. [PMID: 21785958 DOI: 10.1007/s00296-011-2025-5] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2011] [Accepted: 07/10/2011] [Indexed: 11/26/2022]
Abstract
Adult-onset Still's disease (AOSD) patients typically present with arthralgia, fever, lymphadenopathy and a transient salmon maculopapular rash. Only approximately 25 cases of AOSD with urticaria were described in the literature. In this article, the authors report three additional cases of AOSD with urticarial and dermographic lesions who had a good clinical response to glucocorticoid and antihistamines. A review of the literature concerning this issue is also herein written.
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Affiliation(s)
- Paulo Ricardo Criado
- Department of Dermatology, Hospital das Clínicas, Sao Paulo University, Sao Paulo, Brazil.
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29
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Ziemer M, Goetze S, Juhasz K, Elsner P. Flagellate dermatitis as a bleomycin-specific adverse effect of cytostatic therapy: a clinical-histopathologic correlation. Am J Clin Dermatol 2011; 12:68-76. [PMID: 21067249 DOI: 10.2165/11537080-000000000-00000] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
In oncology, bleomycin is a frequently used drug for the treatment of several malignancies. In particular, it is part of chemotherapy protocols in testicular cancer. We report on two patients with testicular cancer who received bleomycin-including chemotherapy and developed flagellate dermatitis. This is a typical adverse effect of bleomycin therapy; however, its pathophysiology has not yet been clarified. We discuss possible pathophysiologic mechanisms for this reaction. In general, it has been postulated that histopathologic findings in flagellate dermatitis share similarities with those observed in fixed drug eruptions. In fact, published cases in the literature have shown a broad variety of histologic changes and the histopathologic investigation of our two patients was not indicative of fixed drug eruption-like changes. Histology of one patient showed a superficial and deep, perivascular and periadnexal infiltrate of lymphocytes and eosinophils with a prominent perisudoral distribution, whereas the other patient was remarkable only for the presence of a rather sparse, superficial, perivascular lymphocytic infiltrate with occasional eosinophils and a few melanophages. Epidermal changes, in particular necrotic keratinocytes, were not present in either patient. We provide an overview of all reported histologic changes in bleomycin-induced flagellate dermatitis, including our experience with two patients. Based on these data, we present a summary of the clinical and histologic features.
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Affiliation(s)
- Mirjana Ziemer
- Department of Dermatology, Venerology and Allergology, University of Leipzig, Germany.
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30
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Fortna RR, Gudjonsson JE, Seidel G, Dicostanzo D, Jacobson M, Kopelman M, Patel RM. Persistent pruritic papules and plaques: a characteristic histopathologic presentation seen in a subset of patients with adult-onset and juvenile Still's disease. J Cutan Pathol 2010; 37:932-7. [PMID: 20546088 DOI: 10.1111/j.1600-0560.2010.01570.x] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
BACKGROUND 'Persistent pruritic papules and plaques' of Still's disease represents a recently described eruption seen in a subset of patients. Most cases reported in the literature to date have been associated with adult-onset Still's disease. METHODS We present the clinical and histopathologic examinations of three female patients ranging in age from 15 to 54 years. RESULTS Our three patients each presented with clinical findings consistent with Still's disease. The youngest patient suffered from the juvenile form of Still's disease (systemic-onset juvenile rheumatoid arthritis). Each patient had a persistent, pruritic eruption with histopathologic findings of dyskeratosis confined to the upper layers of the epidermis as well as a sparse superficial dermal infiltrate containing scattered neutrophils. CONCLUSIONS These cases confirm the characteristic clinical and histopathologic findings of 'persistent papules and plaques of Still's disease' and show the potential for this eruption in both the adult and juvenile age groups.
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Affiliation(s)
- Ryan R Fortna
- Department of Pathology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
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Bagnari V, Colina M, Ciancio G, Govoni M, Trotta F. Adult-onset Still's disease. Rheumatol Int 2009; 30:855-62. [PMID: 20020138 DOI: 10.1007/s00296-009-1291-y] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2009] [Accepted: 11/29/2009] [Indexed: 11/29/2022]
Abstract
Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder characterised by high spiking fever, an evanescent salmon pink rash and arthritis, frequently accompanied by sore throat, myalgias, lymphadenopathies, splenomegaly and neutrophilic leukocytosis. Aetiology is still unknown, however, it seems that an important role is played by various infectious agents, which would act as triggers in genetically predisposed hosts. Diagnosis is a clinical one and may be lengthy because it requires exclusion of infectious neoplasms, including malignant lymphomas and leukaemias, and other autoimmune diseases. Different diagnostic or classification criteria have been proposed, but not definitely accepted. There are no specific laboratory tests for AOSD, but they reflect the systemic inflammation: the ESR is consistently high, while the rheumatoid factors and antinuclear antibodies are negative. High serum ferritin levels associated with a low fraction of its glycosylated component are assessed as useful diagnostic and disease activity markers. The clinical course can be divided into three main patterns with different prognoses: self-limited or monophasic, intermittent or polycyclic systemic and chronic articular pattern. Therapy includes non-steroidal anti-inflammatory drugs, corticosteroids and disease modifying anti-rheumatic drugs: biological agents have recently been introduced and they seem to be very promising not only for the treatment but also for understanding the pathogenic mechanisms underlying the disease.
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Affiliation(s)
- Valentina Bagnari
- Sezione di Reumatologia, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Ferrara, Azienda Sant'Anna, Corso della Giovecca, 203, 44100, Ferrara, Italy.
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Wolgamot G, Yoo J, Hurst S, Gardner G, Olerud J, Argenyi Z. Unique Histopathologic Findings in a Patient With Adult-Onset Still Disease. Am J Dermatopathol 2007; 29:194-6. [PMID: 17414447 DOI: 10.1097/dad.0b013e3180332826] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Adult-onset Still disease (AOSD) is an uncommon disorder characterized by fever, polyarthralgia, elevated white blood cell count, and a maculopapular rash, the histologic features of which have not been well-known. A 55-year-old Asian woman presented initially with a "burning" and severely pruritic eruption on her face, hands, and arms, thought clinically to be urticaria. Within 1 month, she began spiking high fevers, developed diffuse joint pain, and had marked elevations of ferritin, C-reactive protein, and erythrocyte sedimentation rate, characteristic of AOSD. The cutaneous eruption became more widespread, involving the trunk, scalp, and remainder of the extremities, with diffuse thickening of the skin with papular and linear hyperpigmentation and accentuation. Biopsies from several locations showed focal hyperkeratosis associated with dyskeratotic keratinocytes with a peculiar, distinctive distribution in the upper epidermis and cornified layers. In addition, increased dermal mucin was present, with minimal fibroblast proliferation and inflammation. This unusual combination of diffuse dermal mucinosis and a unique pattern of dyskeratosis can present a challenge in generating an accurate differential diagnosis, and may represent an unusual response to chronic scratching or be a distinctive histologic manifestation of AOSD.
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Affiliation(s)
- Greg Wolgamot
- Department of Pathology, University of Washington, Seattle, WA 98195-6100, USA
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Lee JYY, Yang CC, Hsu MML. Histopathology of persistent papules and plaques in adult-onset Still's disease. J Am Acad Dermatol 2006; 52:1003-8. [PMID: 15928619 DOI: 10.1016/j.jaad.2005.02.032] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
BACKGROUND Persistent plaques and linear pigmentation have been reported as specific skin lesions in some patients with adult-onset Still's disease (AOSD). OBJECTIVE We sought to characterize the histologic findings of AOSD-associated persistent rash in 11 cases and correlate the histologic findings with the clinical features. METHODS From 1988 to 2004, 17 cases fulfilling Yamaguchi's criteria for AOSD in our hospital were reviewed and 11 (65%) manifested persistent papules and plaques. The pathology of 13 biopsy specimens of persistent eruption from 9 patients was reviewed. RESULTS The 11 patients consisted of 3 men and 8 women with age of onset ranging from 19 to 67 years (average 34.7 years). Evanescent Still's rash was recorded in 9 patients. The persistent rash manifested as pruritic, red, violaceous, or brownish scaly or crusted lichenoid papules and plaques usually widely distributed over the trunk, neck, face, and extensor sides of the extremities. Lesions arranged in a bizarre linear pattern resulting from scratching were noted in some patients. Three patients died of severe disease, systemic complications, or both. The histology of persistent papules and plaques was characterized by: (1) multiple individual necrotic keratinocytes, singly or in aggregates, mainly located in the upper epidermis, including the normal or parakeratotic horny layer; and (2) infiltration of lymphocytes and neutrophils in the papillary and middermis. Other less common findings included basal vacuolar alteration, nuclear dust, and subcorneal or intracorneal pustules. CONCLUSIONS A clinically and pathologically distinct form of persistent lichenoid eruption was commonly observed in our patients with AOSD. The combination of multiple individual necrotic keratinocytes in the upper epidermis and a dermal infiltrate of neutrophils allow for histologic differentiation of this persistent eruption from most other lichenoid and interface dermatitides and may facilitate an earlier diagnosis of AOSD.
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Affiliation(s)
- Julia Yu-Yun Lee
- Department of Dermatology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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Thien Huong NT, Pitche P, Minh Hoa T, Laurent R. Placards pigmentés fixes au cours de la maladie de Still de l’adulte. Ann Dermatol Venereol 2005; 132:693-6. [PMID: 16230922 DOI: 10.1016/s0151-9638(05)79420-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
Abstract
INTRODUCTION Adult-onset Still's disease (AOSD) is a systemic affection characterized by intermittent fever, evanescent rash, polyarthralgia or arthritis and neutrophilic leucokytosis. We report a new case of AOSD with persistent pigmented plaques in a Vietnamese woman. CASE REPORT A 23 year-old woman had presented within several months: inflammatory polyarthralgia, intermittent fever, asthenia, myalgia, weigh loss, polyadenopathy and an evanescent cutaneous rash. In addition, she presented pigmented skin plaques on the trunk. The investigations noted: neutrophilia (10000/mm3) and a high level of serum ferritin (42,000 microg/l). The erythrocyte sedimentation rate was 55mm in the first hour. C reactive protein was normal. HIV and syphilis serologies, antinuclear antibodies and rheumatoid factor were negative. No growth of micro-organisms was observed in repeated blood and urine cultures. The histology of the persistent plaque and lymph node were not specific. It required a high dose of corticosteroid to obtain remission. DISCUSSION The existence of persistent plaques in AOSD is uncommon. Nevertheless, the exact relationship between the fixed cutaneous lesions and AOSD remains unclear. But their synchronous evolution with systemic symptoms and response to therapy suggest that they represent a specific manifestation of the disease.
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Abstract
INTRODUCTION The diagnosis of adult-onset Still's disease (AOSD) can be very difficult. There are no specific tests and reliance is usually placed on a symptom complex and the well described typical rash seen in most patients. In recent years, however, other cutaneous manifestations of AOSD have been reported but these are not so well known. OBSERVATIONS We report a patient with urticaria and fixed plaques and review the other 'atypical' cutaneous findings associated with AOSD. CONCLUSIONS The diagnosis of AOSD can be made in the absence of the typical Still's rash but in the presence of other atypical cutaneous features.
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Affiliation(s)
- A G Affleck
- Department of Dermatology, Queen's Medical Centre, University Hospital Nottingham NHS Trust, Nottingham, NG7 2UH, UK.
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Prendiville JS, Tucker LB, Cabral DA, Crawford RI. A pruritic linear urticarial rash, fever, and systemic inflammatory disease in five adolescents: adult-onset still disease or systemic juvenile idiopathic arthritis sine arthritis? Pediatr Dermatol 2004; 21:580-8. [PMID: 15461768 DOI: 10.1111/j.0736-8046.2004.21513.x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
The characteristic rash of systemic juvenile idiopathic arthritis is a transient erythematous eruption associated with a quotidian spiking fever. Usually asymptomatic, it can be pruritic, with dermatographism at sites of scratching or pressure. An illness similar to this entity in adults is designated adult-onset Still disease. The relationship between the pediatric and adult disease is uncertain and differences in case definition have evolved. Specifically, a sustained arthritis for at least 6 weeks is required for a diagnosis of systemic juvenile idiopathic arthritis, whereas transient arthritis and arthralgia are accepted criteria in adult-onset Still disease. We describe five patients less than 16 years of age who presented with an acute illness characterized by fever and a distinctive skin eruption. Intense pruritus and linear erythematous lesions flared with a spiking fever, usually in the late afternoon and evening. Periorbital edema/erythema and nonlinear urticarial lesions were also seen. Two children had splinter hemorrhages of the nail beds and one girl developed a fixed, scaling, pigmented, linear eruption. Severe malaise, myalgia, arthralgia, and leukocytosis were present in every patient. Other systemic manifestations included sore throat, transient arthritis, abdominal pain, lymphadenopathy, hepatomegaly, splenomegaly, hyperferritinemia, and hepatic dysfunction. No patient had a sustained arthritis. The course of the disease was variable. One patient, diagnosed with macrophage activation syndrome, recovered on oral naproxen. Two patients responded to systemic corticosteroid therapy. One girl developed status epilepticus and died from aspiration and asphyxia. A boy with severe hepatitis developed renal failure and thrombotic thrombocytopenic purpura and was treated with plasmapheresis, dialysis, and systemic corticosteroids; he had recurrent episodes of rash and fever into adult life. These children did not fulfill the case definition of systemic juvenile idiopathic arthritis because they lacked a persistent arthritis. Adolescent and adult patients with the same clinical and laboratory findings are described under the rubric of adult-onset Still disease. Recognition of the distinctive urticarial skin eruption and spiking fever is important in the diagnosis of a disease with severe morbidity and potentially life-threatening complications.
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Affiliation(s)
- Julie S Prendiville
- Division of Pediatric Dermatology, Department of Pediatrics, British Columbia's Children's Hospital, Vancouver, British Columbia, Canada
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Hamidou MA, Denis M, Barbarot S, Boutoille D, Belizna C, Le Moël G. Usefulness of glycosylated ferritin in atypical presentations of adult onset Still's disease. Ann Rheum Dis 2004; 63:605. [PMID: 15082500 PMCID: PMC1754986 DOI: 10.1136/ard.2003.012484] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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