Abstract
Fever of unknown etiology that occurs along with highly elevated serum ferritin concentrations (>500 ng/mL) is mostly observed in hematologic malignancies and rheumatic diseases such as systemic lupus erythematosus, temporal arteritis, and adult-onset Still's disease (AOSD), among which AOSD is a type of systemic inflammatory disorder with unknown pathophysiology and has very low incidence. AOSD presents with various nonspecific symptoms and signs such as high spiking fever, joint pain, skin rash, and increased leukocytes. Because AOSD is diagnosed after excluding the possibility of other conditions such as neoplasms, infections, and inflammations, diagnosis and treatment are generally delayed. Patients with AOSD often have high serum ferritin levels than those with other conditions, although the underlying mechanism for this is not clearly understood. In addition, decreased proportion of glycosylated ferritin are observed in most patients with AOSD. Therefore a combination of high serum ferritin and a decreased proportion of glycosylated ferritin seems to be important for the differential diagnosis of AOSD that thus may allow early diagnosis of AOSD. Here we report a case of AOSD diagnosed via extremely high serum ferritin levels and decreased glycosylated ferritin proportion.
Figures and Tables
Fig. 1
A markedly increased number of granulocytes and hemophagocytes engulfing neutrophils are noted in the bone marrow aspirate (A, Wright stain, ×1,000) and biopsy specimens (B, H&E stain, ×400). No definite evidence of hemophagocytic lymphohistiocytosis is observed.
![lmo-3-40-g001](/upload/SynapseData/ArticleImage/0192lmo/lmo-3-40-g001.jpg)
Fig. 2
Changes in body temperature, ferritin and C-reactive protein levels during the patient's clinical course.
![lmo-3-40-g002](/upload/SynapseData/ArticleImage/0192lmo/lmo-3-40-g002.jpg)
References
1. Cunha BA, Durie N, Selbs E, Pherez F. Fever of unknown origin (FUO) due to Rosai-Dorfman disease with mediastinal adenopathy mimicking lymphoma: diagnostic importance of elevated serum ferritin levels and polyclonal gammopathy. Heart Lung. 2009. 38:83–88.
![crossref](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
2. Zenone T. Fever of unknown origin in rheumatic diseases. Infect Dis Clin North Am. 2007. 21:1115–1135. x–xi.
![crossref](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
4. Efthimiou P, Paik PK, Bielory L. Diagnosis and management of adult onset Still's disease. Ann Rheum Dis. 2006. 65:564–572.
![crossref](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
5. Yamaguchi M, Ohta A, Tsunematsu T, Kasukawa R, Mizushima Y, Kashiwagi H, et al. Preliminary criteria for classification of adult Still's disease. J Rheumatol. 1992. 19:424–430.
6. Masson C, Le Loet X, Liote F, Dubost JJ, Boissier MC, Perroux-Goumy L, et al. Comparative study of 6 types of criteria in adult Still's disease. J Rheumatol. 1996. 23:495–497.
7. Ramirez C, Rubio C, Fernandez de la Puebla RA, Aguilera C, Espejo I, Fuentes F. Clinical significance of increased serum ferritin levels. Medicina Clinica. 2004. 122:532–534.
8. Akritidis N, Giannakakis Y, Sakkas L. Very high serum ferritin levels in adult-onset Still's disease. Br J Rheumatol. 1997. 36:608–609.
![crossref](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
9. Ota T, Higashi S, Suzuki H, Eto S. Increased serum ferritin levels in adult Still's disease. Lancet. 1987. 1:562–563.
![crossref](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
10. Van Reeth C, Le Moel G, Lasne Y, Revenant MC, Agneray J, Kahn MF, et al. Serum ferritin and isoferritins are tools for diagnosis of active adult Still's disease. J Rheumatol. 1994. 21:890–895.
11. Worwood M, Cragg SJ, Wagstaff M, Jacobs A. Binding of human serum ferritin to concanavalin A. Clin Sci (Lond). 1979. 56:83–87.
![crossref](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
12. Knockaert DC. Recurrent fevers of unknown origin. Infect Dis Clin North Am. 2007. 21:1189–1211. xi
![crossref](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
13. Chen DY, Lan JL, Lin FJ, Hsieh TY. Proinflammatory cytokine profiles in sera and pathological tissues of patients with active untreated adult onset Still's disease. J Rheumatol. 2004. 31:2189–2198.
14. Lee MH, Means RT Jr. Extremely elevated serum ferritin levels in a university hospital: associated diseases and clinical significance. Am J Med. 1995. 98:566–571.
![crossref](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
15. Meijvis SC, Endeman H, Geers AB, ter Borg EJ. Extremely high serum ferritin levels as diagnostic tool in adult-onset Still's disease. Neth J Med. 2007. 65:212–214.
16. Hamidou MA, Denis M, Barbarot S, Boutoille D, Belizna C, Le Moel G. Usefulness of glycosylated ferritin in atypical presentations of adult onset Still's disease. Ann Rheum Dis. 2004. 63:605.
![crossref](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)
17. Fautrel B, Le Moel G, Saint-Marcoux B, Taupin P, Vignes S, Rozenberg S, et al. Diagnostic value of ferritin and glycosylated ferritin in adult onset Still's disease. J Rheumatol. 2001. 28:322–329.
18. Hong AR, Song CH, Lee J, Ma KA, Park CS, Lee CH, et al. Clinical Study on Adult Onset Still's Disease: Analysis in 15 Cases. J Korean Rheum Assoc. 1997. 4:60–69.
19. Lee EB, Song YW. Clinical analysis of adult onset still's disease: 22 cases in Korea. J Korean Rheum Assoc. 1995. 2:52–59.
20. Cho KS, Yoo DH, Yun HR, Lee MH, Lee JK, Shim SC, et al. Adult onset Still's disease: clinical features and prognostic factors in Korea. J Korean Rheum Assoc. 1998. 5:64–75.
21. Yang YS, Shin MK, Hong SJ, Lee YA, Lee MH. Clinical study on adult onset Still's disease. Korean J Dermatol. 2010. 48:388–394.
22. Rogers JT, Bridges KR, Durmowicz GP, Glass J, Auron PE, Munro HN. Translational control during the acute phase response. Ferritin synthesis in response to interleukin-1. J Biol Chem. 1990. 265:14572–14578.
![crossref](/image/icon/bnr_ref_cross.gif)
![crossref](/image/icon/bnr_ref_cross.gif)