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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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Lou J, Zhang X. Atypical cutaneous presentation of AOSD with persistent itchy urticaria: A case report. Medicine (Baltimore) 2023; 102:e36251. [PMID: 38115334 PMCID: PMC10727623 DOI: 10.1097/md.0000000000036251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Accepted: 11/01/2023] [Indexed: 12/21/2023] Open
Abstract
RATIONALE Adult-onset Still's disease (AOSD) is a rare multisystem disorder considered a complex autoinflammatory syndrome. The clinical and biological features of AOSD typically include a high fever with arthritic symptoms, evanescent skin rash, sore throat, striking neutrophilic leukocytosis, hyperferritinemia, and abnormal liver function. The typical rash and fever are important diagnostic clues for AOSD. Here, we report a case of atypical rash manifesting as persistent itchy urticaria. PATIENT CONCERNS A 57-year-old female presented with a 6-day history of fever. During her hospital stay, she progressively developed rashes that were not associated with fever, primarily distributed on her back and the distal extremities, and associated with pronounced itching. The rash was initially suspected to be urticaria; however, the patient exhibited a poor response to antihistamines. After malignancies and other rheumatic diseases were excluded, the diagnosis leaned towards AOSD based on diagnostic criteria. The patient's fever was well controlled with the initiation of glucocorticoids, and no further rashes were observed. DIAGNOSES Although the patient exhibited atypical rashes, after ruling out malignancies and other rheumatic diseases, she met 2 major and 3 minor criteria. Based on Yamaguchi's criteria, the patient was diagnosed with AOSD. INTERVENTIONS Initially, the patient was administered an intravenous infusion of methylprednisolone at 40 mg once daily. This was later transitioned to oral administration with gradual dose reduction. OUTCOMES Follow-up at 1 year showed no recurrence of the rash, with a stable condition and no relapse. LESSONS This case provides valuable insights for the early diagnosis of AOSD, emphasizing the importance of considering this diagnosis even when presenting with atypical skin rash.
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Affiliation(s)
- Jingfeng Lou
- Department of General Medicine, Chengdu Second People’s Hospital, Chengdu, China
| | - Xingping Zhang
- Department of General Medicine, Chengdu Second People’s Hospital, Chengdu, China
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Daghor-Abbaci K, Ait Hamadouche N, Makhloufi CD, Mechid F, Otmani F, Makrelouf M, Otmane A, Smail N, Boucelma M, Aissat FZ, Lefkir-Teffiani S, Bengana B, Boukheris N, Tebaibia A, Taharbouchet B, Ayoub S, Benziane B, Oumnia N, Haouichet C, Hanni F, Laraba N, Hakem D, Benfenatki N, Berrah A. Proposal of a new diagnostic algorithm for adult-onset Still's disease. Clin Rheumatol 2023; 42:1125-1135. [PMID: 36694091 DOI: 10.1007/s10067-023-06509-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Revised: 12/30/2022] [Accepted: 01/05/2023] [Indexed: 01/26/2023]
Abstract
OBJECTIVE This study was performed to develop a new diagnostic algorithm for adult-onset Still's disease (AOSD). METHODS We conducted a multicenter prospective nationwide case-control study in tertiary Internal Medicine, Rheumatology, and Infectious Diseases departments, to include successively patients with suspected AOSD based on the presence of two or more major criteria of Yamaguchi and/or Fautrel classifications. Patients were classified as AOSD or controls according to a predefined procedure. A receiving operating characteristic curve was used to determine the best cutoff value of the points-based score for disease classification. A diagnostic algorithm was developed to help the physician in the diagnostic approach. RESULTS A total of 160 patients were included, 80 patients with AOSD and 60 controls with different diagnoses. Twenty patients with incomplete data were excluded. In the multivariate analysis, 6 items remained independently associated with AOSD diagnosis: typical rash (OR: 24.01, 3 points), fever ≥ 39 °C (OR: 17.34, 3 points), pharyngitis (OR: 10.23, 2 points), arthritis (OR: 9.01, 2 points), NLR ≥ 4 (OR: 11.10, 2 points), and glycosylated ferritin ≤ 20% (OR: 1.59, 1 point). AOSD should be considered if the patient satisfies 7 points with a sensitivity of 92.5%, specificity of 93.3%, and accuracy of 92.8% (area under the curve (AUC): 0.97 [95% CI: 0.94-0.99]). The present points-based score was more accurate and sensitive than the Yamaguchi classification (78.8%, 92.5%, p = 0.01) and Fautrel classification (76.3%, 92.5%, p = 0.004). A typical rash associated with a points-based score ≥ 7 points leads to a very likely disease. CONCLUSION The proposed new algorithm could be a good diagnostic tool for adult-onset Still's disease in clinical practice and research. Key Points • A diagnostic algorithm was performed to help the physician in the diagnostic approach of AOSD. • The points-based score included in this algorithm had a high sensitivity and accuracy. • This diagnostic algorithm can be useful in the clinical research.
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Affiliation(s)
- Karima Daghor-Abbaci
- Internal Medicine Department, University of Algiers 1, Faculty of Medical Sciences, Benyoucef Benkhedda, Bab El Oued University Hospital Center, 16000, Bab El Oued City, Algiers, Algeria. .,Biochemistry, Hemotology and Genetics Laboratory of Research, Bab El Oued University Hospital Center, Bab El Oued City, Algiers, Algeria.
| | - Nadia Ait Hamadouche
- Department of Epidemiology, Bab El Oued University Hospital Center, Bab El Oued City, Algiers, Algeria
| | - Chafia Dahou Makhloufi
- Rheumatology Department, Bab El Oued University Hospital Center, Bab El Oued City, Algiers, Algeria
| | - Farida Mechid
- Rheumatology Department, Bab El Oued University Hospital Center, Bab El Oued City, Algiers, Algeria
| | - Fifi Otmani
- Internal Medicine Department, Mustapha Bacha University Hospital Center, 1st May City, Algiers, Algeria
| | - Mohamed Makrelouf
- Biochemistry, Hemotology and Genetics Laboratory of Research, Bab El Oued University Hospital Center, Bab El Oued City, Algiers, Algeria
| | - Amel Otmane
- Biochemistry, Hemotology and Genetics Laboratory of Research, Bab El Oued University Hospital Center, Bab El Oued City, Algiers, Algeria
| | - Nourredine Smail
- Department of Epidemiology, Mustapha Bacha University Hospital Center, 1st May City, Algiers, Algeria
| | - Malika Boucelma
- Internal Medicine Department, Kouba University Hospital Center, Kouba City, Algiers, Algeria
| | - Fatma Zohra Aissat
- Infectious Diseases Department, El Hadi Flici University Hospital Center, Casbah City, Algiers, Algeria
| | - Salima Lefkir-Teffiani
- Rheumatology Department, Benimessous University Hospital Center, Algiers, Benimessous City, Algeria
| | - Bilel Bengana
- Rheumatology Department, Benimessous University Hospital Center, Algiers, Benimessous City, Algeria
| | - Nadia Boukheris
- Internal Medicine Department, Annaba University Hospital Center, Annaba City, Algeria
| | - Amar Tebaibia
- Internal Medicine Department, Birtraria University Hospital Center, El Biar City, Algiers, Algeria
| | - Baya Taharbouchet
- Internal Medicine Department, Bouloughine University Hospital Center, Algiers, Bouloughine City, Algeria
| | - Soraya Ayoub
- Internal Medicine Department, Benimessous University Hospital Center, Algiers, Benimessous City, Algeria
| | - Brahim Benziane
- Internal Medicine Department, Laghouat University Hospital Center, Laghouat City, Algeria
| | - Nadia Oumnia
- Internal Medicine Department, Zmirli University Hospital Center, El Harrache City, Algiers, Algeria
| | - Chafika Haouichet
- Rheumatology Department, Douera University Hospital Center, Blida City, Algeria
| | - Fella Hanni
- Rheumatology Department, Benaknoun University Hospital Center, Benaknoun City, Algiers, Algeria
| | - Nazim Laraba
- Internal Medicine Department, University of Algiers 1, Faculty of Medical Sciences, Benyoucef Benkhedda, Bab El Oued University Hospital Center, 16000, Bab El Oued City, Algiers, Algeria
| | - Djennete Hakem
- Internal Medicine Department, Mostaghanem University Hospital Center, Mostaghanem City, Algeria
| | - Nacera Benfenatki
- Internal Medicine Department, Rouiba University Hospital Center, Rouiba City, Algiers, Algeria
| | - Abdelkrim Berrah
- Internal Medicine Department, University of Algiers 1, Faculty of Medical Sciences, Benyoucef Benkhedda, Bab El Oued University Hospital Center, 16000, Bab El Oued City, Algiers, Algeria
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Whittington C, Lapides R, Morley K, Greene L. Persistent, Pruritic, Reddish-Brown Papules and Plaques: An Atypical Presentation of Adult-Onset Still’s Disease. Cureus 2023; 15:e35587. [PMID: 37007372 PMCID: PMC10062437 DOI: 10.7759/cureus.35587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/27/2023] [Indexed: 03/04/2023] Open
Abstract
Adult-onset Still's disease (AOSD) is a systemic inflammatory condition characterized by recurrent fevers and a dermatologic eruption. The eruption is classically described as migratory and evanescent, composed of salmon-pink to erythematous macules, patches, and papules. However, a much rarer skin rash can also be seen in the setting of AOSD. This eruption has a different morphology, appearing as fixed, extremely pruritic papules and plaques. The histology of this atypical form of AOSD is distinct from that of the more common evanescent eruption. Management of AOSD is multi-faceted, aimed at controlling both the acute and chronic phases. Increased awareness of this more uncommon cutaneous presentation of AOSD is vital so that the appropriate diagnosis can be rendered. Herein, the authors describe an atypical presentation of AOSD in a 44-year-old male patient who presented with persistent, pruritic, brownish papules and plaques on the trunk and extremities.
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Daghor Abbaci K, Ait Hamadouche N, Otmani F, Dahou Makhloufi C, Mechid F, Makrelouf M, Otmane A, Smail N, Boucelma M, Aissat FZ, Lefkir-Teffiani S, Bengana B, Boukheris N, Tebaibia A, Taharbouchet B, Ayoub S, Benziane B, Oumnia N, Haouichet C, Hanni F, Laraba N, Hakem D, Benfenatki N, Berrah A. Validation of the neutrophil-to-lymphocyte ratio as a new simple biomarker of adult onset Still's disease: A STROBE-Compliant prospective observational study. Medicine (Baltimore) 2022; 101:e29970. [PMID: 35960098 PMCID: PMC9371519 DOI: 10.1097/md.0000000000029970] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
This study was performed to investigate the role of neutrophil-to-lymphocyte ratio (NLR) in the diagnosis of adult onset Still disease (AOSD) and its performance to improve the sensitivity of the classifications criteria (Yamaguchi and Fautrel Classifications). We conducted a multicenter prospective nationwide case-control study in Internal medicine, Rheumatology and Infectious disease departments, to include successively patients with suspected AOSD (2 or more major criteria of Yamaguchi or Fautrel classifications). All clinical and biological features were collected in a consensual and standardized clinical assessment at baseline and during follow-up. A receiving operating characteristic (ROC) curve was used to reassess the cutoff value of NLR. After determination of the cutoff value for NLR by ROC curve, 2 composite sets (Yamaguchi classification + NLR as a major criterion and Fautrel classification + NLR as a major criterion) were performed and evaluated. One hundred sixty patients were included, 80 patients with AOSD and 60 controls with different diagnoses. Twenty patients with incomplete data were excluded. The cutoff value for NLR equals 4 (area under the curve, AUC: 0.82). The NLR was ≥ 4 in 93.7% (75/80) of AOSD patients with a sensitivity of 93.8% and specificity of 61.7%. The association of NLR as a major criterion with the classification of Yamaguchi or Fautrel improved their sensitivity, respectively for Fautrel (76.3% to 92.5%, P = .004) and Yamaguchi (78.8% to 90%, P = .05). This study validates the NLR as a good simple biomarker of AOSD with a cutoff value of 4 and high sensitivity (93.8%). The addition of NLR (NLR ≥ 4) as a major criterion to the classifications (Yamaguchi and Fautrel) improved significantly their sensitivity and accuracy.
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Affiliation(s)
- Karima Daghor Abbaci
- Internal Medicine Department, University of Algiers 1, Faculty of Medical Sciences, Benyoucef Benkhedda, Bab El Oued University Hospital Center, Bab El Oued city, Algiers, Algeria
- Biochemistry, Hemotology and Genetics Laboratory of Research, Bab El Oued University Hospital Center, Bab El Oued City, Algiers Algeria
- * Correspondence: Karima Daghor Abbaci, Department of Internal medicine, University of Algiers 1, Faculty of Medical sciences, Benyoucef Benkhedda, Bab El Oued University Hospital center, Bab El Oued City, 16 000, Algiers, Algeria, North Africa (e-mail: )
| | - Nadia Ait Hamadouche
- Department of epidemiology, Bab El Oued University Hospital Center, Bab El Oued city, Algiers, Algeria
| | - Fifi Otmani
- Internal Medicine Department, Mustapha Bacha University Hospital Center, 1st May City, Algiers, Algeria
| | - Chafia Dahou Makhloufi
- Rheumatology department, Bab El Oued University Hospital center, Bab El Oued city, Algiers, Algeria
| | - Farida Mechid
- Rheumatology department, Bab El Oued University Hospital center, Bab El Oued city, Algiers, Algeria
| | - Mohamed Makrelouf
- Biochemistry, Hemotology and Genetics Laboratory of Research, Bab El Oued University Hospital Center, Bab El Oued City, Algiers Algeria
| | - Amel Otmane
- Biochemistry, Hemotology and Genetics Laboratory of Research, Bab El Oued University Hospital Center, Bab El Oued City, Algiers Algeria
| | - Nourredine Smail
- Department of Epidemiology, Mustapha Bacha University Hospital Center, 1st May City, Algiers, Algeria
| | - Malika Boucelma
- Internal Medicine Department, Kouba University Hospital center, Kouba City, Algiers, Algeria
| | - Fatma Zohra Aissat
- Infectious Diseases Department, El Hadi Flici University Hospital Center, Casbah City, Algiers, Algeria
| | - Salima Lefkir-Teffiani
- Rheumatology Department, Benimessous University Hospital Center, Benimessous City, Algiers, Algeria
| | - Bilel Bengana
- Internal Medicine Department, Annaba University Hospital Center, Annaba City, Algeria
| | - Nadia Boukheris
- Internal Medicine Department, Annaba University Hospital Center, Annaba City, Algeria
| | - Amar Tebaibia
- Internal Medicine Department, Birtraria University Hospital Center, El Biar City, Algiers, Algeria
| | - Baya Taharbouchet
- Internal Medicine Department, Bouloughine University Hospital Center, Bouloughine City, Algiers, Algeria
| | - Soraya Ayoub
- Internal Medicine Department, Benimessous University Hospital Center, Benimessous City, Algiers, Algeria
| | - Brahim Benziane
- Internal Medicine Department, Laghouat University Hospital center, Laghouat City, Algeria
| | - Nadia Oumnia
- Internal Medicine Department, Zmirli University Hospital Center, El Harrache City, Algiers, Algeria
| | - Chafika Haouichet
- Rheumatology Department, Douera University Hospital Center, Blida city, Algeria
| | - Fella Hanni
- Rheumatology Department, Benaknoun University Hospital Center, Benaknoun City, Algiers, Algeria
| | - Nazim Laraba
- Internal Medicine Department, University of Algiers 1, Faculty of Medical Sciences, Benyoucef Benkhedda, Bab El Oued University Hospital Center, Bab El Oued city, Algiers, Algeria
| | - Djennete Hakem
- Internal Medicine Department, Mostaghanem University Hospital Center, Mostaghanem City, Algeria
| | - Nacera Benfenatki
- Internal Medicine Department, Rouiba University Hospital Center, Rouiba City, Algiers, Algeria
| | - Abdelkrim Berrah
- Internal Medicine Department, University of Algiers 1, Faculty of Medical Sciences, Benyoucef Benkhedda, Bab El Oued University Hospital Center, Bab El Oued city, Algiers, Algeria
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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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A case of adult-onset Still's disease accompanied with pulmonary tuberculosis successfully treated with colchicine. Postepy Dermatol Alergol 2021; 38:912-915. [PMID: 34849145 PMCID: PMC8610067 DOI: 10.5114/ada.2021.110105] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Accepted: 05/26/2020] [Indexed: 11/17/2022] Open
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Abstract
Adult-onset Still’s disease is a rare inflammatory disorder usually affecting young adults. Elderly-onset Still’s disease (EOSD) is reported in some cases, commonly in Japan, the USA and Europe. One of the most commonly used criteria for diagnosing EOSD is Yamaguci criteria. In elderly patients more severe course of the disease and more complications may be expected than in the younger group of patients with Still’s disease. The lungs involvement is rather rare manifestation of this disease. In our article we discuss the problem of both the development of Still’s disease in the elderly and interstitial lung changes in the course of the disease, based on available literature and own cases from one centre.
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Daghor KA, Berrah A. Melanoderma in adult-onset Still's disease. Rheumatology (Oxford) 2021; 61:1299. [PMID: 34022035 DOI: 10.1093/rheumatology/keab458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 05/14/2021] [Indexed: 11/13/2022] Open
Affiliation(s)
- Karima Abbaci Daghor
- Internal Medicine Department, Bab El Oued University Hospital Centre, University of Algiers 1 Benyoucef Benkhedda, Algiers, Algeria
| | - Abdelkrim Berrah
- Internal Medicine Department, Bab El Oued University Hospital Centre, University of Algiers 1 Benyoucef Benkhedda, Algiers, Algeria
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Adult onset Still's disease in the elderly: a case-based literature review. BMC Rheumatol 2021; 5:12. [PMID: 33875007 PMCID: PMC8056719 DOI: 10.1186/s41927-021-00183-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 02/16/2021] [Indexed: 11/20/2022] Open
Abstract
Background Adult onset Still’s disease (AOSD) is a rare inflammatory disorder that classically presents with high spiking fevers, evanescent rash, and arthritis. The diagnosis is one of exclusion and can be further complicated by atypical presentations, particularly in elderly patients in whom AOSD is very rare. Case presentation A case of AOSD in a 73-year-old woman with a non-classic presentation, leading to delayed diagnosis and management, is presented along with a review of the English literature for AOSD cases in elderly people over 70 years of age. Thirty nine case reports and series were identified and the current case was added, totaling 42 individual cases. Significant findings included a four-times higher prevalence in females, a higher prevalence of macrophage activation syndrome despite lower mortality, the presence of pruritic rash in almost one fifth of the cases, and high prevalence of delayed diagnosis. Conclusions AOSD in the elderly may vary from the classic criteria described in the medical literature and may lead to delayed diagnosis and management. Further evaluation and better characterization of AOSD in the elderly remains an area of interest.
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Maeda-Aoyama N, Hamada-Ode K, Taniguchi Y, Nishikawa H, Arii K, Nakajima K, Fujimoto S, Terada Y. Dyskeratotic cells in persistent pruritic skin lesions as a prognostic factor in adult-onset Still disease. Medicine (Baltimore) 2020; 99:e19051. [PMID: 32028422 PMCID: PMC7015626 DOI: 10.1097/md.0000000000019051] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Adult-onset Still disease (AOSD), a systemic inflammatory disorder, is characterized by high fever, evanescent rash, arthritis, and hyperferritinaemia. AOSD is also reported to be associated with other skin lesions, including persistent pruritic papules and plaques. This study aimed to assess the significance of dyskeratotic skin lesions in Japanese AOSD patients.We retrospectively assessed the histology of persistent pruritic skin lesions and evanescent rashes and the relationship between dyskeratotic cells, serum markers, and outcomes in 20 Japanese AOSD patients, comparing AOSD histology with that of dermatomyositis (DM), drug eruptions, and graft-versus-host disease (GVHD).As the results, Persistent pruritic lesions were characterized by scattered single keratinocytes with an apoptotic appearance confined to the upper layer of the epidermis and horny layer without inflammatory infiltrate. In contrast to AOSD, the histology of DM, drug eruption, and GVHD demonstrated dyskeratotic cells in all layers of the epidermis with inflammatory infiltrate. AOSD with evanescent rash showed no dyskeratotic cells. The dyskeratotic cells in pruritic AOSD lesions stained positive for ssDNA and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, indicating apoptosis. Serum IL-18 was significantly higher in AOSD patients with dyskeratotic cells than those without, and generally required higher doses of glucocorticoids, immunosuppressants, and biologic agents. Two of ten AOSD patients with dyskeratotic cells died from hemophagocytic lymphohistiocytosis.In conclusion, Persistent pruritic AOSD skin lesions are characterized by dyskeratotic cells with apoptotic features, involving the upper layers of the epidermis. There may be a link to elevated IL-18. This dyskeratosis may be a negative prognostic indicator.
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Affiliation(s)
- Natsuki Maeda-Aoyama
- Department of Endocrinology, Metabolism, Nephrology and Rheumatology, Kochi Medical School Hospital, Nankoku
| | - Kazu Hamada-Ode
- Department of Endocrinology, Metabolism, Nephrology and Rheumatology, Kochi Medical School Hospital, Nankoku
| | - Yoshinori Taniguchi
- Department of Endocrinology, Metabolism, Nephrology and Rheumatology, Kochi Medical School Hospital, Nankoku
| | - Hirofumi Nishikawa
- Department of Endocrinology, Metabolism, Nephrology and Rheumatology, Kochi Medical School Hospital, Nankoku
| | - Kaoru Arii
- Department of Internal Medicine, Kochi Red Cross Hospital, Kochi
| | - Kimiko Nakajima
- Department of Dermatology, Kochi Medical School Hospital, Nankoku, Japan
| | - Shimpei Fujimoto
- Department of Endocrinology, Metabolism, Nephrology and Rheumatology, Kochi Medical School Hospital, Nankoku
| | - Yoshio Terada
- Department of Endocrinology, Metabolism, Nephrology and Rheumatology, Kochi Medical School Hospital, Nankoku
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Fernandez-Flores A. La biopsia cutánea en el contexto de la enfermedad sistémica. ACTAS DERMO-SIFILIOGRAFICAS 2019; 110:710-727. [DOI: 10.1016/j.ad.2019.02.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 02/11/2019] [Accepted: 02/12/2019] [Indexed: 02/07/2023] Open
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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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15
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Vitale A, Cavalli G, Colafrancesco S, Priori R, Valesini G, Argolini LM, Baldissera E, Bartoloni E, Cammelli D, Canestrari G, Sota J, Cavallaro E, Massaro MG, Ruscitti P, Cipriani P, De Marchi G, De Vita S, Emmi G, Ferraccioli G, Frassi M, Gerli R, Gremese E, Iannone F, Lapadula G, Lopalco G, Manna R, Mathieu A, Montecucco C, Mosca M, Piazza I, Piga M, Pontikaki I, Romano M, Rossi S, Rossini M, Silvestri E, Stagnaro C, Talarico R, Tincani A, Viapiana O, Vitiello G, Galozzi P, Sfriso P, Gaggiano C, Rigante D, Dagna L, Giacomelli R, Cantarini L. Long-Term Retention Rate of Anakinra in Adult Onset Still's Disease and Predictive Factors for Treatment Response. Front Pharmacol 2019; 10:296. [PMID: 31001115 PMCID: PMC6454864 DOI: 10.3389/fphar.2019.00296] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2018] [Accepted: 03/11/2019] [Indexed: 12/13/2022] Open
Abstract
Background: Anakinra (ANA) is an effective treatment choice in patients with adult onset Still's disease (AOSD). Variables affecting treatment survival include loss of efficacy or adverse events, but also the decision to discontinue treatment after long-term clinical remission. Objectives: Aims of this study were: (i) to assess the drug retention rate (DRR) of ANA during a long-term follow-up looking for any difference related to the line of biologic treatment, the concomitant use of conventional disease modifying anti-rheumatic drugs (cDMARDs) and the different type of AOSD (systemic versus chronic articular); (ii) to identify predictive factors of lack of efficacy, loss of efficacy, and ANA withdrawal owing to long-term remission. Methods: AOSD patients classified according with Yamaguchi criteria and treated with ANA were retrospectively enrolled in 18 Italian tertiary Centers. Demographic, laboratory, clinical and therapeutic data related to the start of ANA (baseline), the 3-month assessment and the last follow-up visit while on ANA treatment were retrospectively collected and statistically analyzed. Results: One hundred and forty-one AOSD patients (48 males, 93 females) treated with ANA for a mean period of 35.96 ± 36.05 months were enrolled. The overall DRR of ANA was 44.6 and 30.5% at the 60- and 120-month assessments, respectively, with no significant differences between: (i) biologic naïve patients and those previously treated with other biologics (log-rank p = 0.97); (ii) monotherapy and concomitant use of cDMARDs (log-rank p = 0.45); (iii) systemic and chronic articular types of AOSD (log-rank p = 0.67). No variables collected at baseline could predict primary inefficacy, while the number of swollen joints at baseline was significantly associated with secondary inefficacy (p = 0.01, OR = 1.194, C.I. 1.043-1.367). The typical AOSD skin rash was negatively related with ANA withdrawal owing to long-term remission (p = 0.03, OR = 0.224, C.I. 0.058-0.863). Conclusion: Long-term DRR of ANA has been found excellent and is not affected by different lines of biologic treatment, concomitant use of cDMARDs, or type of AOSD. The risk of losing ANA efficacy increases along with the number of swollen joints at the start of therapy, while the typical skin rash is a negative predictor of ANA withdrawal related to sustained remission.
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Affiliation(s)
- Antonio Vitale
- Research Centre of Systemic Autoinflammatory Diseases, Behçet’s Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Centre, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
| | - Giulio Cavalli
- Vita-Salute San Raffaele University, Milan, Italy
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Serena Colafrancesco
- Rheumatology Unit, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Roberta Priori
- Rheumatology Unit, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Guido Valesini
- Rheumatology Unit, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | | | - Elena Baldissera
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Elena Bartoloni
- Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, Italy
| | - Daniele Cammelli
- Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy
| | - Giovanni Canestrari
- Institute of Rheumatology and Affine Sciences, Division of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy
| | - Jurgen Sota
- Research Centre of Systemic Autoinflammatory Diseases, Behçet’s Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Centre, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
| | - Elena Cavallaro
- Department of Medical and Biological Sciences, Rheumatology Clinic, University of Udine, Udine, Italy
| | - Maria Grazia Massaro
- Periodic Fever Research Center, Institute of Internal Medicine, Catholic University of the Sacred Heart, Fondazione Policlinico A. Gemelli, Rome, Italy
| | - Piero Ruscitti
- Department of Biotechnological and Applied Clinical Science, Division of Rheumatology, University of L’Aquila, L’Aquila, Italy
| | - Paola Cipriani
- Department of Biotechnological and Applied Clinical Science, Division of Rheumatology, University of L’Aquila, L’Aquila, Italy
| | - Ginevra De Marchi
- Department of Medical and Biological Sciences, Rheumatology Clinic, University of Udine, Udine, Italy
| | - Salvatore De Vita
- Department of Medical and Biological Sciences, Rheumatology Clinic, University of Udine, Udine, Italy
| | - Giacomo Emmi
- Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy
| | - Gianfranco Ferraccioli
- Institute of Rheumatology and Affine Sciences, Division of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy
| | - Micol Frassi
- Rheumatology and Clinical Immunology, Spedali Civili and Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Roberto Gerli
- Rheumatology Unit, Department of Medicine, University of Perugia, Perugia, Italy
| | - Elisa Gremese
- Institute of Rheumatology and Affine Sciences, Division of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy
| | - Florenzo Iannone
- Rheumatology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - Giovanni Lapadula
- Rheumatology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - Giuseppe Lopalco
- Rheumatology Unit, Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
| | - Raffaele Manna
- Periodic Fever Research Center, Institute of Internal Medicine, Catholic University of the Sacred Heart, Fondazione Policlinico A. Gemelli, Rome, Italy
| | - Alessandro Mathieu
- Rheumatology Unit, Department of Medical Sciences, University and AOU of Cagliari, Cagliari, Italy
| | - Carlomaurizio Montecucco
- Department of Rheumatology, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
| | - Marta Mosca
- Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Ilaria Piazza
- Rheumatology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Matteo Piga
- Rheumatology Unit, Department of Medical Sciences, University and AOU of Cagliari, Cagliari, Italy
| | | | - Micol Romano
- Division of Rheumatology, ASST Gaetano Pini, Milan, Italy
| | - Silvia Rossi
- Department of Rheumatology, IRCCS Policlinico San Matteo Foundation, University of Pavia, Pavia, Italy
| | - Maurizio Rossini
- Rheumatology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Elena Silvestri
- Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy
| | - Chiara Stagnaro
- Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Rosaria Talarico
- Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Angela Tincani
- Rheumatology and Clinical Immunology, Spedali Civili and Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Ombretta Viapiana
- Rheumatology Unit, Department of Medicine, University of Verona, Verona, Italy
| | - Gianfranco Vitiello
- Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy
| | - Paola Galozzi
- Department of Medicine DIMED, Rheumatology Unit, University of Padua, Padua, Italy
| | - Paolo Sfriso
- Department of Medicine DIMED, Rheumatology Unit, University of Padua, Padua, Italy
| | - Carla Gaggiano
- Clinical Pediatrics, Department of Molecular Medicine and Development, University of Siena, Siena, Italy
| | - Donato Rigante
- Institute of Pediatrics, Università Cattolica Sacro Cuore, Fondazione Policlinico Universitario A. Gemelli I.R.C.C.S., Rome, Italy
| | - Lorenzo Dagna
- Vita-Salute San Raffaele University, Milan, Italy
- Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR), IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Roberto Giacomelli
- Department of Biotechnological and Applied Clinical Science, Division of Rheumatology, University of L’Aquila, L’Aquila, Italy
| | - Luca Cantarini
- Research Centre of Systemic Autoinflammatory Diseases, Behçet’s Disease Clinic and Rheumatology-Ophthalmology Collaborative Uveitis Centre, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy
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16
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Ito Y, Takeichi T, Koide T, Akiyama M. Case of adult-onset Still's disease with psoriasiform eruptions. J Dermatol 2018; 46:e109-e110. [PMID: 30144140 DOI: 10.1111/1346-8138.14613] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Affiliation(s)
- Yasutoshi Ito
- Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takuya Takeichi
- Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Toshiko Koide
- Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masashi Akiyama
- Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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17
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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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18
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Brance ML, Neffen EL. Oral mucosa lesions as atypical manifestation of adult-onset Still´s disease. An Bras Dermatol 2018; 93:271-273. [PMID: 29723378 PMCID: PMC5916405 DOI: 10.1590/abd1806-4841.20186836] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2016] [Accepted: 06/18/2017] [Indexed: 11/22/2022] Open
Abstract
Adult-onset Still's disease is a systemic inflammatory disorder of unknown etiology, characterized by skin rash, spiking fever, arthralgias or arthritis, and leukocytosis. The typical skin rash is evanescent, salmon-pink, nonpruritic and maculopapular, predominantly on the extremities. It is considered one of the major Yamaguchi's criteria in adult-onset Still's disease. However, atypical skin lesions are also described. Here, a 61-year-old woman with sore throat, spiking fever, polyarthritis and evanescent salmon-pink nonpruritic maculopapular skin rash on the extremities was diagnosed with adult-onset Still's disease. In addition, atypical brown macules on oral mucosa, localized on the inner lips and tongue were also observed. Biopsy revealed a neutrophilic infiltrate. Despite treatment and improvement of the adult-onset Still's disease, the atypical oral mucosal lesions persisted.
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Affiliation(s)
- María Lorena Brance
- Rheumatology Centre - Rosario, Argentina
- Bone Biology Laboratory. School of Medicine, Universidad Nacional
de Rosario- Rosario, Argentina
- National Council of Scientific and Technical Research (CONICET) -
Rosario, Argentina
| | - Eldo Luis Neffen
- Pathological Anatomy Deparment, Clínica Pergamino -
Pergamino, Argentina
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19
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Takeichi T, Watanabe N, Muro Y, Teshigawara S, Sato M, Ban N, Akiyama M. Phosphorylated signal transducer and activator of transcription 3 in the epidermis in adult-onset Still's disease. J Dermatol 2017; 44:1172-1175. [PMID: 28470759 DOI: 10.1111/1346-8138.13888] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2016] [Accepted: 03/20/2017] [Indexed: 11/28/2022]
Abstract
Adult-onset Still's disease (AOSD) is characterized by multiple systemic inflammation of unknown etiology. Although the typical eruption of AOSD is salmon-pink rheumatoid rash on the trunk and extremities, persistent pruritic papules and plaques have also been reported. Correlations between serum cytokines, including interleukin-6 and -18, and disease activity in AOSD have been reported. Activated signal transducer and activator of transcription 3 (STAT3) is transported into the nucleus, where it functions as a transcription factor that regulates genes involved in cell survival and inflammation. To assess whether STAT3 was phosphorylated in skin samples from AOSD patients, we conducted immunohistochemical analysis of affected and unaffected lesions from four AOSD patients in comparison with 10 normal controls. Quantitative analysis was conducted by measuring the ratio of epidermal keratinocytes with phosphorylated STAT3 (p-STAT3)-positive nuclei to total epidermal keratinocytes. p-STAT3 was found to be more strongly expressed in the nuclei in the epidermis of AOSD than in normal controls. Quantification of the data revealed significant differences in staining for p-STAT3 between AOSD and normal skin. Our findings suggest that phosphorylation of STAT3 may be a potential therapeutic target for AOSD.
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Affiliation(s)
- Takuya Takeichi
- Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Naoki Watanabe
- Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yoshinao Muro
- Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Shiho Teshigawara
- Department of General Medicine/Family and Community Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Motoki Sato
- Department of General Medicine/Family and Community Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Nobutaro Ban
- Department of General Medicine/Family and Community Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masashi Akiyama
- Department of Dermatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
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20
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Santa E, McFalls JM, Sahu J, Lee JB. Clinical and histopathological features of cutaneous manifestations of adult-onset Still disease. J Cutan Pathol 2017; 44:591-595. [PMID: 28342280 DOI: 10.1111/cup.12935] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2017] [Revised: 03/18/2017] [Accepted: 03/21/2017] [Indexed: 01/05/2023]
Abstract
Adult-onset Still disease (AOSD) is a rare autoinflammatory syndrome characterized by recurring fevers, arthralgia, and consistent laboratory abnormalities that include leukocytosis and hyperferritinemia. Skin findings accompany the disease in nearly 90% of the cases. Early reports described evanescent, pruritic, salmon-pink or urticarial lesions, referred to as the typical eruption of AOSD. Histopathologic findings consist of superficial perivascular dermatitis with varying number of interstitial neutrophils. Later reports described a more persistent rash that tended to be photodistributed, hyperpigmented, often in a linear configuration, sometimes in a rippled pattern, referred to as the atypical eruption of AOSD. The presence of individual necrotic keratinocytes in the upper spinous layer has been the consistent histopathologic finding. The persistent rash may not represent an atypical presentation of AOSD as recent reports indicate a high prevalence of the rash. Emerging data also suggest that patients with persistent eruption have a worse prognosis. The recognition of the clinical and histopathological findings of skin eruptions of AOSD may facilitate an earlier diagnosis, potentially improving disease outcome. Herein, clinical and histopathological features of cutaneous manifestation of AOSD in 2 Asian women are highlighted accompanied by a relevant review of the disease.
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Affiliation(s)
- Erin Santa
- Bryn Mawr Dermatology (private practice), Villanova, Pennsylvania
| | - Jeanne M McFalls
- Department of Pathology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
| | - Joya Sahu
- Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Jason B Lee
- Department of Dermatology and Cutaneous Biology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania
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21
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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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22
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Agha-Abbaslou M, Bensaci AM, Dike O, Poznansky MC, Hyat A. Adult-Onset Still's Disease: Still a Serious Health Problem (a Case Report and Literature Review). AMERICAN JOURNAL OF CASE REPORTS 2017; 18:119-124. [PMID: 28154368 PMCID: PMC5302814 DOI: 10.12659/ajcr.901846] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Patient: Female, 53 Final Diagnosis: Adult-onset Still’s Disease Symptoms: Abdominal pain • fever Medication: — Clinical Procedure: — Specialty: Rheumatology
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Affiliation(s)
- Mojgan Agha-Abbaslou
- Division of Infectious Disease, Department of Medicine, Vaccine and Immunotherapy Center, Massachusetts General Hospital, Boston, MA, USA
| | - Ana Maria Bensaci
- Division of Infectious Disease, Department of Medicine, Salem Hospital, North Shore Medical Center, Salem, MA, USA
| | - Oluchi Dike
- Department of Internal Medicine, Salem Hospital, North Shore Medical Center, Salem, MA, USA
| | - Mark C Poznansky
- Division of Infectious Disease, Department of Medicine, Vaccine and Immunotherapy Center, Massachusetts General Hospital, Boston, MA, USA
| | - Arooj Hyat
- Department of Internal Medicine, Salem Hospital, North Shore Medical Center, Salem, MA, USA
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23
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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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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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Marinova M, Nabergoj M, Artusi C, Zaninotto MM, Plebani M. A Case of Atypical Urticaria. Clin Chem 2016; 62:558-60. [DOI: 10.1373/clinchem.2015.243220] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2015] [Accepted: 08/31/2015] [Indexed: 11/06/2022]
Affiliation(s)
| | - Mitja Nabergoj
- Hematology and Clinical Immunology, University-Hospital, Padova, Italy
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26
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Atypical Cutaneous Manifestations in Adult Onset Still's Disease. Case Rep Rheumatol 2016; 2016:4835147. [PMID: 26981304 PMCID: PMC4770116 DOI: 10.1155/2016/4835147] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2015] [Revised: 01/18/2016] [Accepted: 01/19/2016] [Indexed: 11/17/2022] Open
Abstract
Adult Onset Still's Disease (AOSD), an adult variant of systemic onset juvenile idiopathic arthritis, is a rare systemic inflammatory disorder of unknown aetiology. The rarity of this disease is associated with low index of suspicion and delayed diagnosis in patients suffering from it and in the presence of atypical features the diagnosis can be further challenging. This is a case report on a 24-year-old woman, who was a diagnostic dilemma for 2 years due to the nonspecific symptoms of recurrent fever, generalized maculopapular persistent pruritic and tender rash, and polyarthralgia. She was initially diagnosed as leukocytoclastic vasculitis on a skin biopsy and was managed by a dermatologist with various medications including NSAIDs, hydroxychloroquine, dapsone, colchicine, cyclosporine, and high doses of oral steroids with minimal response. Subsequently, she has had multiple admissions with similar symptoms with raised inflammatory markers and negative septic workup. On one occasion, her iron study revealed hyperferritinaemia which led to the suspicion of AOSD. Once the rheumatic fever and infectious, malignant, autoimmune, and lymphoproliferative disorders were excluded, she was diagnosed as probable AOSD and managed successfully with IL-1 (interleukin-1) receptor antagonist, Anakinra, with remarkable and lasting response both clinically and biochemically.
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27
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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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28
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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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29
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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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