Adult-onset Still disease (AOSD), commonly referred in the literature as the adult form of systemic-onset juvenile idiopathic arthritis, is a disorder of unknown etiology [1] [2]. The clinical presentation might be quite different from patient to patient, but the following manifestations are included in the diagnostic criteria [1] [3] [4] [5]:

• Fever - Although not specific, the recurring appearance of very high fever (> 39°C) that lasts for a few hours and mainly happens in the late afternoon or early evening period, is a hallmark of AOSD [3] [6].
• Joint pain - The involvement of knees, wrists, or ankles is another important manifestation of AOSD [3] [4]. Arthritis usually accompanies fever and has a relatively short duration as well [3].
• Rash - A salmon-pink or erythematous nonpruritic maculopapular rash, developing together with fever and joint pain, is frequently observed, and is most commonly seen on the trunk and the proximal limbs [5].

Other common manifestations of AOSD are lymphadenopathy, hepatosplenomegaly, muscle aches, and pharyngitis [1] [7]. The clinical course of the disorder can be highly variable, ranging from mild and self-limiting to severely debilitating disease [3]. Furthermore, AOSD may cause a myriad of complications in affected individuals, such as pulmonary hypertension, thrombotic thrombocytopenic purpura (TTP), amyloidosis, and macrophage activation syndrome [1]. An early detection of this disorder could significantly aid in successful treatment and improvement of the overall quality of life.

• Splenomegaly

  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 [ncbi.nlm.nih.gov]

  – Elevated acute-phase reactants: elevated ESR, CRP, white count, and hyperferritinemia (69-97% of patients) -Other findings that may be found include: myalgia, sore throat, hepatomegaly, splenomegaly, lymphadenopathy, serositis, abdominal pain, elevated [utswim.wordpress.com]

• Generalized Lymphadenopathy

  Definition / general Rare systemic inflammatory disease accompanied by a triad of spiking fever, maculopapular exanthema and arthralgia, accompanied frequently by lymphadenopathy Essential features Fever, skin rash, joint pains, lymphadenopathy with paracortical [pathologyoutlines.com]

  Other characteristic manifestations include a prodromal sore throat, arthralgias, myalgias, weight loss, serositis, hepatomegaly (often with elevated hepatic enzymes), splenomegaly and generalized lymphadenopathy. [rheumnow.com]

  It differs from classical rheumatoid arthritis in that it is more often marked by acute febrile onset, and generalized lymphadenopathy and hepatosplenomegaly are more prominent. [icd10data.com]

  B (Minor criteria) comprises (i) TLC > or = 15000/mm 3 (ii) Still's rash (iii) Pleuritis or pericarditis (iv) Hepatomegaly or splenomegaly or generalized lymphadenopathy. Our patient qualified for all criteria from A and two criteria from B. [ijnm.in]

  On examination, she looked pale, febrile (temperature 39.2ºC), had non-suppurative pharyngitis and generalized lymphadenopathy. The lymph nodes were slightly tender, small and discrete. [pjms.com.pk]

• Fever

  Arthritis usually accompanies fever and has a relatively short duration as well. [symptoma.com]

  We describe five patients less than 16 years of age who presented with an acute illness characterized by fever and a distinctive skin eruption. [ncbi.nlm.nih.gov]

  The duration of fever is telltale and may last 1-3 days (familial Mediterranean fever, CAPs, Muckle Wells) or 5-21 days (TRAPS) or daily (AOSD, SoJIA, Schnitzler syndrome). [rheumnow.com]

• Lymphadenopathy

  Adult-onset Still disease is an idiopathic systemic disorder that presents with relapsing high fever, joint pain, skin rash, pharyngitis, hepatosplenomegaly, and lymphadenopathy. [symptoma.com]

  Definition / general Rare systemic inflammatory disease accompanied by a triad of spiking fever, maculopapular exanthema and arthralgia, accompanied frequently by lymphadenopathy Essential features Fever, skin rash, joint pains, lymphadenopathy with paracortical [pathologyoutlines.com]

  A 33 year old Hispanic male presented with recurrent daily fevers, sore throat and lymphadenopathy. Diagnostic evaluation including lymph node biopsy was negative for infectious causes. [oatext.com]

  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, [ncbi.nlm.nih.gov]

• High Fever

  Adult-onset Still disease is an idiopathic systemic disorder that presents with relapsing high fever, joint pain, skin rash, pharyngitis, hepatosplenomegaly, and lymphadenopathy. [symptoma.com]

  A 48-year-old woman was admitted because of spiking high fever, sore throat, and jaundice. [ncbi.nlm.nih.gov]

  Major diagnostic criteria include arthralgia for more than 2 weeks, intermittent high fever for more than 1 week, characteristic rash, and white blood cell count above 10,000. [orpha.net]

• Anemia

  AOSD patients with RHS showed higher frequencies of leukopenia, anemia, thrombocytopenia, hypoalbuminemia, hypofibrinogenemia, hypertriglyceridemia, hyperferritinemia, and elevated lactate dehydrogenase levels than did those without RHS. [ncbi.nlm.nih.gov]

  Autoimmune hemolytic anemia. Nihon Rinsho 2008;66:520–523. 15. Pirofsky B. Clinical aspects of autoimmune hemolytic anemia. Semin Hematol 1976;13:251–265. [synapse.koreamed.org]

  METHODS: Previously we developed a method to measure the iron content of ferritin; we investigated the usefulness of this method to establish the iron status of patients with anemia of inflammation. [jrheum.org]

  […] inflammatory disease manifesting with spiking fever, sore throat, arthralgia, skin rash and hepatosplenomegaly Reactive hemophagocytic syndrome is also reported Diagnosis Clinical, laboratory and imaging results Laboratory Neutrophilic leukocytosis, anemia [pathologyoutlines.com]

• Swinging Fever

  By day 10 of her illness she was admitted to hospital with a “fever of unknown origin”. In hospital it was found that she had swollen joints, a high swinging fever and blood tests that were consistent with severe inflammation. [nras.org.uk]

• Pharyngitis

  Adult-onset Still disease is an idiopathic systemic disorder that presents with relapsing high fever, joint pain, skin rash, pharyngitis, hepatosplenomegaly, and lymphadenopathy. [symptoma.com]

  Arthritis (OR, 8.6; 95% confidence interval [CI], 1.5-49.1; p = 0.014), pharyngitis (OR, 6.9; 95% CI, 1.5-30.2; p = 0.010), splenomegaly (OR, 5.4; 95% CI, 1.1-26.7; p = 0.039), and neutrophilic leukocytosis (OR, 18.1; 95% CI, 3.5-93.6; p = 0.001) were [ncbi.nlm.nih.gov]

  Pharyngitis Pharyngitis, non-suppurative occurs in approximately 70% of the patients [ 6 ]. Hepatomegaly with or without elevation in liver aminotransferases frequently occurs. [oapublishinglondon.com]

  Clinical features include quotidian fevers, arthralgias, arthritis, pharyngitis, lymphadenopathy and an evanescent rash. AOSD should be considered in the differential diagnosis of fever of unknown origin. [pagepress.org]

  Pharyngitis is often the initial symptom. Keywords Juvenile Idiopathic Arthritis Interstitial Lung Disease Familial Mediterranean Fever Juvenile Rheumatoid Arthritis Serum Ferritin Level These keywords were added by machine and not by the authors. [link.springer.com]

• Nausea

  Poor appetite, nausea, and weight loss may occur. Lymphadenopathy, splenomegaly, hepatomegaly, and sore throat are also common. Pericarditis, pleuritis, pericardial effusion and pleural effusion may occur but is less likely. [slideshare.net]

  Poor appetite, nausea, and weight loss are common. There is also commonly swelling of the lymph glands, enlargement of the spleen and liver, and sore throat. [rxlist.com]

• Hepatomegaly

  Physical examination revealed pallor, hepatomegaly. [ijnm.in]

  – Elevated acute-phase reactants: elevated ESR, CRP, white count, and hyperferritinemia (69-97% of patients) -Other findings that may be found include: myalgia, sore throat, hepatomegaly, splenomegaly, lymphadenopathy, serositis, abdominal pain, elevated [utswim.wordpress.com]

  Other systemic manifestations included sore throat, transient arthritis, abdominal pain, lymphadenopathy, hepatomegaly, splenomegaly, hyperferritinemia, and hepatic dysfunction. No patient had a sustained arthritis. [ncbi.nlm.nih.gov]

• Hepatosplenomegaly

  Adult-onset Still disease is an idiopathic systemic disorder that presents with relapsing high fever, joint pain, skin rash, pharyngitis, hepatosplenomegaly, and lymphadenopathy. [symptoma.com]

  […] interferon gamma and tumor necrosis factor alpha may play a role May also be due to genetic factors, immune dysfunction and infections Clinical features Systemic inflammatory disease manifesting with spiking fever, sore throat, arthralgia, skin rash and hepatosplenomegaly [pathologyoutlines.com]

  Adult onset Still's disease (AOSD) is a systemic inflammatory disease characterized by high-fevers, articular involvement, maculopapular rash, hepatosplenomegaly, lymphadenopathy, and a neutrophilic leukocytosis. [ncbi.nlm.nih.gov]

  HLH is also characterized by fever, hepatosplenomegaly, increased ferritin levels all of which are also features of AOSD. [ijpmonline.org]

  There was no hepatosplenomegaly or lymphadenopathy. [cureus.com]

• Periorbital Edema

  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. [ncbi.nlm.nih.gov]

  Da-Lim Yoon, Seohyun Lee, So Young Park, You Jae Kim, Bon San Koo, Min Wook So, Yong-Gil Kim, Chang-Keun Lee and Bin Yoo, A Case of Adult-Onset Still's Disease Presenting with Periorbital Edema, Journal of Rheumatic Diseases, 20, 4, (243), (2013). [doi.org]

• Arthritis

  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. [ncbi.nlm.nih.gov]

  Juvenile idiopathic arthritis "Adult-onset Still's disease". Genetic and Rare Diseases Information Center (GARD). [en.wikipedia.org]

• Arthralgia

  AOSD, although uncommon, has a characteristic constellation of clinical and laboratory features and should be considered in the differential diagnosis of pyrexia of unknown origin associated with a rash and arthralgia. [e-ijd.org]

  Severe malaise, myalgia, arthralgia, and leukocytosis were present in every patient. [ncbi.nlm.nih.gov]

  Arthralgia is usually correlated with fever spikes. [orpha.net]

  PMN predominant. – Arthralgias: With or without synovitis. Occurs in 72-95% of patients. [utswim.wordpress.com]

• Myalgia

  Five weeks earlier, sore throat, fever, malaise, and myalgias had developed. Broad-spectrum antibiotic therapy was administered, without improvement. A diagnosis was made. [blogs.nejm.org]

  Since March 2017, he has had progressive fatigue, myalgias, rash, weight loss, diarrhea, and recurrent low-grade fever. Subsequent bone marrow biopsy and FDG PET/CT demonstrated no active lymphoma. [ncbi.nlm.nih.gov]

  Adult Onset Still’s disease (AOSD) is a multisystemic inflammatory disorder of unknown etiology characterized by spiking fever, skin rash, arthralgia/arthritis and myalgia. [stillsdisease.org]

• Skin Rash

  Current diagnostic criteria are divided into major (Fever ≥ 39°C, joint pain, skin rash, pharyngitis, granulocytosis of ≥ 80%, and glycosylated ferritin fraction of ≤ 20%) and minor (leukocytosis of > 10,000/mm3 and a typical skin rash). [symptoma.com]

  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. [ncbi.nlm.nih.gov]

  Abstract Adult onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology characterized by spiking fever, evanescent skin rash, arthralgia or arthritis, involvement of various organs, and predominantly neutrophilic leucocytosis [e-ijd.org]

  Definition / general Rare systemic inflammatory disease accompanied by a triad of spiking fever, maculopapular exanthema and arthralgia, accompanied frequently by lymphadenopathy Essential features Fever, skin rash, joint pains, lymphadenopathy with paracortical [pathologyoutlines.com]

• Eruptions

  We describe five patients less than 16 years of age who presented with an acute illness characterized by fever and a distinctive skin eruption. [ncbi.nlm.nih.gov]

• Koebner Phenomenon

  It commonly appears on the trunk, neck, or extremities and may be associated with dermatographism, Koebner phenomenon (lesions arising at sites of trauma/pressure), pruritus, or urticaria. Fixed dermal plaques have been rarely described. [rheumaknowledgy.com]

  In one-third of patients, the rash is mildly pruritic and develops at sites of pressure or trauma (Koebner’s phenomenon). Arthralgia/Arthritis and Myalgia Intense arthralgias are a universal finding. [stillsdisease.org]

  Look for the rash in areas subject to pressure like the beltline and under the breasts or it can be elicited by stroking the skin (Koebner’s phenomenon). The rash is frequently misdiagnosed as a drug reaction. Figure 1. [clinicaladvisor.com]

  This type of eruption often had a linear configuration, possibly because of the Koebner phenomenon, thus resembling a flagellate erythema. [journals.lww.com]

  Cutaneous manifestations of AOSD: The common ones are Still’s Rash, Koebner phenomenon, Dermatographism. Uncommon: It includes Pruritis, Urticaria, Dermal plaques, Facial Rash, Alopecia, Erythema nodosumd and Raynaud’s phenomenon. [pjms.com.pk]

• Hyperpigmentation

  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. [ncbi.nlm.nih.gov]

  At a late stage of the process, histopathologic features of PP are indistinguishable from any other disease that resolves with postinfammatory hyperpigmentation. [pjms.com.pk]

• Eczema

  Allergic Eczema... Academy of Nutrition and Dietetics The food you eat determines the quality of your life. It affects your appearance, may prevent some diseases... [doi.org]

The diagnosis of AOSD is primarily a one of exclusion, as numerous autoimmune, malignant, and infectious diseases induce the nonspecific signs and symptoms seen in this condition [1] [3] [7] [8]. Thus, a comprehensive clinical and laboratory workup is necessary. Firstly, during a history taking, patients should be asked about the course of the disease and the appearance of symptoms, whereas a thorough physical examination has an important role in identifying lymphadenopathy, cutaneous changes, joint inflammation, and hepatosplenomegaly.

A complete blood count (CBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum ferritin should be evaluated in laboratory studies [1] [3] [4] [7] [8]. Additionally, rheumatoid factor (RF) and antinuclear antibodies (ANA), both performed to exclude conditions such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), are also recommended in the initial workup [3].

Current diagnostic criteria are divided into major (Fever ≥ 39°C, joint pain, skin rash, pharyngitis, granulocytosis of ≥ 80%, and glycosylated ferritin fraction of ≤ 20%) and minor (leukocytosis of > 10,000/mm3 and a typical skin rash) [3] [4] [7] [8]. AOSD is confirmed if ≥ 4 major criteria or 3 major and 2 minor criteria are met [1] [3] [4] [7].

• Thrombocytosis

  Both patients had marked leukocytosis with neutrophil predominance, thrombocytosis, elevated liver enzymes and elevated acute phase rectants. [ajol.info]

  A peripheral smear also showed neutrophilia and thrombocytosis. [ijdvl.com]

  Blood cell count for improvement in leukocytosis and thrombocytosis. [clinicaladvisor.com]

  Investigations revealed hemoglobin of 9.7 g/dL, polymorphonuclear leukocytosis total leukocyte count (TLC 17500/mm 3 with 92% neutrophils), thrombocytosis (platelet count 848000/mm 3 ), a markedly raised erythrocyte sedimentation rate (ESR) (45 mm in [ijnm.in]

  Neutrophilic leukocytosis (WBC > 12.5), thrombocytosis, markedly elevated ESR (50% are >90 mm/hr and 90% are > 50 mm/hr) or C-reactive protein levels (> 2.0 mg/dl). [rheumaknowledgy.com]

• Listeria Monocytogenes

  monocytogenes meningitis in a patient receiving etanercept for Still’s disease, Clin Exp Rheumatol, 2005, vol. 23 pg. 121 28 Adalimumab (anti-TNF-alpha) therapy to improve the clinical course of adult-onset Still’s disease: the first case report, Clin [doi.org]

Treatment failed in four cases (two with each anti-TNF-α) [ 15 ]. [doi.org]

Medications that block the action of interleukin-1, such as anakinra, can be effective treatments when standard steroid treatments are insufficient. [en.wikipedia.org]

Tocilizumab (TCZ) was added to his treatment, which resulted in a rapid remission. This case suggests the usefulness of TCZ in the treatment of severe AOSD with CP and pleuritis. [ncbi.nlm.nih.gov]

[…] depends on the specific disease pattern Overall, patients with only localized disease have a better prognosis compared to those with more disseminated disabilities or severe complications Disease can be monocyclic - self limiting, polycyclic - symptoms [pathologyoutlines.com]

Prognosis The overall prognosis is generally good, once acute life-threatening manifestations have been controlled. Some patients with chronic disease and major joint involvement may have significantly altered quality of life. [orpha.net]

Systemic manifestations, per se, did not contribute to poor functional prognosis. Chronic articular disease had the worst outcome: 27% evolved to functional class III status, compared with none in the cyclic systemic groups. [ncbi.nlm.nih.gov]

What is the Prognosis of Adult-Onset Still’s Disease? (Outcomes/Resolutions) The prognosis of Adult-Onset Still’s Disease may be assessed on a case-by-case basis. [dovemed.com]

The disease is an entity with heterogeneous pathology; and diverse suggested etiologies, clinical manifestations and prognoses. [ncbi.nlm.nih.gov]

Abstract Adult onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology characterized by spiking fever, evanescent skin rash, arthralgia or arthritis, involvement of various organs, and predominantly neutrophilic leucocytosis [e-ijd.org]

Etiology The etiology of AOSD and its underlying pathogenetic mechanisms are not known. No risk factors for the disease have been identified so far, but environmental factors are suspected. [orpha.net]

Our study aims to analyze different aspects of articular manifestations complicating adult onset Still disease to define epidemiological, clinical and evolving characteristics of these complications. [panafrican-med-journal.com]

[…] disease accompanied by a triad of spiking fever, maculopapular exanthema and arthralgia, accompanied frequently by lymphadenopathy Essential features Fever, skin rash, joint pains, lymphadenopathy with paracortical hyperplasia and immunoblastic reaction Epidemiology [pathologyoutlines.com]

Summary Epidemiology Prevalence and incidence data are difficult to determine given the broad, non-specific clinical presentation. The estimated prevalence of AOSD is more than 1/100,000 population. [orpha.net]

Magadur-Joly G et al (1995) Epidemiology of adult Still’s disease: estimate of the incidence by a retrospective study in west France. Ann Rheum Dis 54(7):587–590 PubMed CrossRef Google Scholar 4. [doi.org]

References Magadur-Joly G, Billaud E, Barrier JH, Pennec YL, Masson C, et al. (1995) Epidemiology of adult Still's disease: estimate of the incidence by a retrospective study in west France. Ann Rheum Dis 54: 587. [archivesofmedicine.com]

Recent accumulation of knowledge, mostly arising from hereditary autoinflammatory diseases and from the systemic-onset juvenile idiopathic arthritis (sJIA), has given raise to new hypotheses on the pathophysiology of AOSD. [ncbi.nlm.nih.gov]

Pathophysiology is yet to be clearly defined Interleukins, macrophage colony stimulating factor, interferon gamma and tumor necrosis factor alpha may play a role May also be due to genetic factors, immune dysfunction and infections Clinical features [pathologyoutlines.com]

More important, novel biologic therapies have offered important clues to AOSD's underlying pathophysiology. [dovepress.com]

Additional research into the pathophysiology of PNGD is also warranted, as this would optimize medical management. [archivesofmedicine.com]

Autoinflammatory syndromes and cellular responses to stress: pathophysiology, diagnosis and new treatment perspectives. Best Pract Res Clin Rheumatol. 2012;26:505–33. PubMed CrossRef Google Scholar 52. [doi.org]

Clinicians need to be aware of this condition so that they can correctly diagnose it and prevent its serious complications. [ncbi.nlm.nih.gov]

It is important to keep the inflammation under control to prevent more damage to the body. If prednisone is taken for a long time, a doctor may recommend taking calcium and vitamin D to prevent thinning of the bones. [arthritis.org]

When steroids are used they will often be given with other drugs to help to prevent side-effects. [nras.org.uk]

REFERENCE BOOK Screening for Colorectal Cancer | CTFPHC REFERENCE BOOK Screening for Cognitive Impairment | CTFPHC REFERENCE BOOK Screening for Depression | CTFPHC REFERENCE BOOK Screening for Developmental Delay | CTFPHC Review Canadian Task Force on Preventive [qxmd.com]

Treatment aims to control inflammation, and prevent joint damage and other complications. [rarediseases.info.nih.gov]

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