Clinical diagnosis
Case 208
【Progress】
He was given other non-steroid anti-inflammatory drugs. However, they were not sufficient to abate so that he was administered steroid pulse therapy
【Discussion】
Clinical diagnosis of Adult’s Still disease should be made by the diagnosis of exclusion. It is because the similar symptoms occur by the other diseases: malignant lymphoma, polymyalgia rheumatica (PMR), remittent seronegative symmetric synovitis with pitting edema (R3SPE), systemic lupus erythematosus. The major symptoms of Adult’s Still disease are: spike fever of 39°C, salmon pink eruption, arthritis (swollen joint, joint pain), muscle pain and pleuritis & carditis (1-4). The characteristics of laboratory test are high values of; white blood cells especially neutrophils; ferritin; interleukin 2 (1-4). In our case, he experienced eruption on the fore arm, arthritis, muscle pain, and fever of 37.6°C under NSAIDs administration, which seemed not contradictory to satisfy the major symptoms. Further, in laboratory test, WBC 22960/mm3, serum ferritin > 5000 ng/ dL (20-280), and interleukin 2R 2600 U/mL (157-474) were found. Chest CT showed pleural effusion and pericardial suffusion. These data met the criteria of Adult’s Still disease.
Etiology of Sill disease irrespective of Adult or Juvenile is still unknown. There are two speculations; triggered disease following microbes infection based on the fact ongoing infection such as pharyngitis often occurs: pure autoimmune disease.
The mechanism of marked elevation of ferritin is not fully clarified. Macrophages stimulated by inflammation produce interleukin 6 which effect on hepcidin, resulting in ferritin production from liver which is one of the greatest Fe storage organs (5). Other report said that ferritin is produced by macrophages themselves (6). It is speculated that macrophages urge to prepare for virtual anemia against inflammation. Ferritin becomes much higher level in Still disease rather than other inflammatory diseases.
Values of three interleukins elevate in Still disease: Interleukin 2, Interleukin 6 and Interleukin 18. Interleukin 2 is secreted by helper T cell and functions proliferation and activation of natural killer T cell, macrophages, monocytes and B cells which produce antibody. Interleukin 6 secretes from macrophages and induces acute response to acute inflammation. Interleukin 18 is produced by macrophages and dendric cells and makes to transform naïve T cell into natural killer cell working together with interferon γ (7, 8).
Interleukin 6 is an inflammatory cytokine produced by macrophages and brings about leukocytes coming in the vessels, inducing acute response to inflammation. It means Still disease is similar to sepsis and seems to be caused by microorganisms rather than autoimmune disease. When interleukin 6 and/or other cytokines from hyper-leukocytosis becomes higher level, it causes endothelial dysfunction and makes thrombosis working together platelets accumulation (7). As a result, macrophages response excessively to something, leading to Still disease. In our case, leukocytosis and thrombocytosis occur, inducing elevation of D-dimer. D dimer is a part of FDP. In our case, leukocytosis, thrombocytosis and elevation of D-dimer were found, indicative of susceptible to thrombosis.
【Summary】
We present a seventy two-year-old male for muscle pain, wrist arthritis, skin eruption. Laboratory test revealed CRP 29.85 mg/dL, WBC 22960/mm3, platelet 482000/mm3, D-dimer 14.8μg, serum ferritin > 5000 ng/dL (20-280), AST 78 IU, ALT 91 IU, creatinine 1.11 mg/dL, and interleukin 2R 2600 U/mL (157-474). The clinical findings and the data of laboratory test seemed to be compatible with diagnosis of Adult’s Still disease. It is borne in mind that major symptoms of Still disease are muscle pain, spike fever over 39°C, salmon pink eruption, pericarditis & pleuritis. The laboratory data shows elevation of leukocytosis, ferritin, Interleukin 2, interleukin 6 and Interleukin 12. Further, pleural effusion and pericarditis occur in 40 % of Still disease. Thrombocytosis and D dimer elevation also are found because of endothelial damage due to cytokine from leukocytes. As a result, macrophages response excessively to something, leading to Still disease.
【References】
1.Gerfaud-Valentin, et al. "Adult-onset Still's disease". Autoimmunity Reviews. 2014;13:708–722.
2.Stéphane M, et al.. "Complications of adult-onset Still's disease and their management". Expert Review of Clinical Immunology. 2018; 14: 351–365.
3.Antoine N, et al. (2018-04-11). "Diagnostic and management of life-threatening Adult-Onset Still Disease: a French nationwide multicenter study and systematic literature review". Critical Care
2018; 22 :88. doi:10.1186/s13054-018-2012-2. ISSN 1466-609X. PMC 5896069. PMID 29642928.
4.Jamilloux, Y, et al. "Pathogenesis of adult-onset Still's disease: new insights from the juvenile counterpart". Immunologic Research.2015; 61: 53-62
5.Wang W, Knovich MA, Coffman LG, Torti FM, Torti SV. "Serum ferritin: Past, present and future". Biochimica et Biophysica Acta (BBA) - General Subjects. 2010;1800 : 760–769.
6.Cristina R et al. The Hyperferritinemic Syndrome: macrophage activation syndrome, Still’s disease, septic shock and catastrophic antiphospholipid syndrome. J Clin Rheumatol. 2013;19:324-328.
7.Suwa T, et al. Interleukin-6 induces demargination of intravascular neutrophils and shortens their transit in marrow. Am J Physiol Heart Circ Physiol. 2000;279:2954-2960.
8.Colafrancesco, S, et al. IL-18 Serum Level in Adult Onset Still's Disease: A Marker of Disease Activity. Int J Inflam. 2012; 2012: 156890. Published online 2012 Jun 18. doi: 10.1155/2012/156890
2020.10.14