2 criteria + 3 main symptoms, master the diagnosis of Still disease

*It is only for medical professionals to read for reference.
The cause is not clear, how to diagnose? The 2021 American Academy of Rheumatology Annual Meeting (ACR 2021), as the most influential academic feast gathering the latest research on rheumatism and immunity, has attracted attention at home and abroad
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Still's disease is a group of autoinflammatory diseases, mainly manifested by high fever, joint pain, and skin rash
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However, the etiology is not clear, and the diagnosis is still difficult
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Professor Bella Mehta from Cornell University School of Medicine discussed the "Diagnosis of Still Disease" and explained the clinical manifestations, diagnostic criteria and disease burden of Still Disease, which helped us to remove the fog of Still Disease
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Still disease-auto-inflammation? self-immune? Stupidly confused Still's disease is a group of rare autoinflammatory diseases, divided by age, Still's disease includes systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (adult-onset Still's disease) , AOSD)
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Its etiology and pathogenesis are not yet clear, and may be related to heredity, immunity, and infection
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Figure 1 Auto-inflammatory disease VS autoimmune disease First of all, it is necessary to clarify the difference between autoimmune disease and auto-inflammatory disease
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Autoinflammatory diseases mainly involve the innate immune system such as macrophages and monocytes, while autoimmune diseases involve the acquired immune system such as T cells and B cells
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Still’s disease has many similarities with autoinflammatory diseases, such as the absence of pathogenic microorganisms, autoantibodies, antigen-specific T cells, etc.
, and it has similar clinical features to autoinflammatory diseases such as familial Mediterranean fever.
At the same time, it has features of fever.
In terms of single gene mutation and duration of exacerbation, Still's disease is also different from traditional autoinflammatory diseases
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Therefore, we believe that Still disease is between autoimmune diseases and autoinflammatory diseases
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Over time, we have gradually realized that sJIA and AOSD may have the same pathogenesis.
AOSD is considered to be the continuation of sJIA in adulthood, but at the same time they have some differences
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Figure 2 The difference between sJIA and AOSD The male to female ratio of sJIA is 1:1, while the male to female ratio of AOSD is 3:7, and adult women are more susceptible
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Adults are more likely to have sore throat symptoms, and the incidence of sJIA is much higher than that of adults, but the mortality rate of adults is higher
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The clinical manifestations of Still's disease-three main symptoms, multiple side symptoms, fever, skin rash, arthralgia/arthritis are the main clinical symptoms and signs of adult Still's disease
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Fever is the most prominent symptom of this disease, which is seen in almost all patients and often runs through the entire disease process
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The most common type of heat is continuous relaxation fever, with a body temperature of up to 39°C to 40°C, and there may be 1 to 2 peaks in a day, and it can return to normal without treatment
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It can also show missing heat or irregular heat type
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Skin rash is another common clinical manifestation of this disease.
About 85% of patients can have orange-red macules or maculopapular rash, urticaria, erythema nodosa, and purpura, mainly distributed in the proximal limbs, neck and trunk
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The rash appears more often than in high fever, and the fever disappears and is transient, leaving no traces after it subsides
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Fig.
3 The rash of Still’s disease arthralgia/arthritis is another main symptom of this disease, which is often accompanied by fever.
It is aggravated by high fever and relieved after fever.
Any joint can be affected.
Commonly involved joints are the knee, wrist, and ankle.
, Shoulders, elbows, proximal interphalangeal joints, metacarpophalangeal joints, and distal interphalangeal joints may also be affected
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Repeatedly affected joints can gradually develop aggressive arthritis, leading to ankylosis and limited mobility of the affected joints
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Figure 4 X-ray manifestations of Still's disease (left: sJIA; right: AOSD) In ​​the early stage of the disease, 70% of patients may have sore throat, which worsens with fever and relieves fever
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Pharyngeal hyperemia, hyperplasia of lymphatic follicles and swollen tonsils on the posterior pharyngeal wall can be seen, but the pharyngeal swab culture is negative and antibiotic treatment is ineffective
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Lymph node enlargement, hepatosplenomegaly, abdominal pain, pleurisy, pericardial effusion, myocarditis, and pneumonia can also be seen in this disease
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Nervous system disease and kidney damage are rare.
A small number of severe patients may have acute liver failure, respiratory failure, congestive heart failure, diffuse intravascular coagulation, and hemophagocytic syndrome
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Still’s disease has three disease modes, namely single-circulation type (30%), multi-circulation type (30%), and chronic arthritis type (40%): (1) Single-circulation type refers to a typical attack of more than 2 months.
After treatment, long-term remission can be achieved, and the prognosis is good; (2) Multi-circulation type refers to the repeated recurrence of the disease, but the recurrence symptoms are milder than the first symptoms, and gradually achieve complete remission; (3) Chronic arthritis type is disease activity and joint symptoms persist Exist, joint destruction may occur in severe cases
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Understanding disease patterns is essential for early diagnosis and treatment
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Figure 5 The clinical manifestations of the three disease modes of Still's disease are difficult to distinguish, and auxiliary examinations are used to help imaging: X-ray shows uniform cartilage loss, similar to the erosion foci of rheumatoid arthritis (RA), joint space narrowing, and joint stiffness , Especially the carpal bones, without periostitis can be distinguished from psoriatic arthritis
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Figure 6 The pros and cons of the three imaging examinations.
Laboratory examinations: the diagnosis of this disease lacks specific antibodies.
Laboratory examinations of 90% of patients showed an increase in the total number of peripheral blood white blood cells, mainly neutrophils, and an increase in platelet counts in half of the patients.
Can be combined with positive cell positive pigment anemia
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C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are significantly increased during acute inflammation.
Serum ferritin is helpful for the diagnosis of the disease.
It is significantly increased during the active period of the disease and can be used as an indicator of disease activity and detection of therapeutic effects
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The biomarkers currently used in clinical diagnosis of AOSD include ESR, CRP and serum ferritin, and many emerging AOSD biomarkers are under study, such as glycoferritin, interleukin (IL-1, IL-6, IL-18, IL- 37), heme oxygenase -1 (HO-1), calprotectin, neutrophils - lymphocytes ratio, and the like transcriptomics
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Although these biomarkers have not yet been applied clinically, AOSD will definitely have more sensitive and specific biomarkers in the near future
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A variety of methods are on the battlefield, and the diagnostic criteria set the world.
Because the disease lacks specific diagnosis and evaluation criteria, most of them adopt differential diagnosis methods, and the manifestations of the disease are also very heterogeneous.
The clinical manifestations of different individuals are different.
This caused a delay in diagnosis
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Studies have shown that the average diagnosis delay is 3-4 months, but some patients can even reach 20 years
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The current diagnostic criteria include Cush criteria, Yamaguchi criteria and Feutrel criteria
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Figure 7 Cush criteria Yamaguchi criteria: main criteria: fever ≥39℃ and lasting more than 1 week; arthritis/arthralgia lasting more than 2 weeks; typical rash; white blood cells ≥10×109/L and more than 80% are polymorphonuclear leukocytes
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Secondary criteria: sore throat; lymph node and/or splenomegaly; abnormal liver function; negative rheumatoid factor and antinuclear antibody
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Exclusion criteria: Exclude neoplastic diseases, infectious diseases and other rheumatic diseases
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Meeting 5 or more (at least 2 of the main criteria must be) can be considered for diagnosis of adult Still disease
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 Fautrel criteria: Main criteria: fever ≥39℃; arthralgia; transient skin erythema; pharyngitis; polymorphonuclear leukocytes ≥80%; glycosylated ferritin ≤20%
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Secondary criteria: skin maculopapular rash; white blood cells ≥10×10°/L
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The diagnosis of this disease is considered when meeting ≥4 major criteria or 3 major criteria + 2 minor criteria
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 Differential diagnosis: The diseases that need to be differentiated include viral infections, reactive arthritis, other systemic rheumatism (such as dermatomyositis), hematopoietic syndrome, and hematological malignancies
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Menacing complications, individual medical advantages, patients with Still disease have a higher physical and mental burden.
Studies have shown that the anxiety and depression scores of patients with active AOSD are significantly higher than those of inactive patients.
During 2009-2013, 5820 AOSD patients in the United States were hospitalized , The average length of hospital stay is 7-13 days, and the cost is 30,000-66,000 US dollars, which brings a greater economic burden to patients
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AOSD may have serious, life-threatening complications
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A study involving more than 5,000 AOSD patients in the United States showed that 1.
7% of patients developed macrophage activation syndrome, 1.
1% developed diffuse intravascular coagulation, 0.
4% developed thrombotic thrombocytopenic purpura, and even 2.
6% of patients eventually developed Death
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In addition, other studies have shown that AOSD can be combined with severe infections and acute respiratory distress syndrome
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Figure 8 MAS is related to increased mortality.
One of the most serious and life-threatening complications is macrophage activation syndrome (MAS).
When the disease of AOSD patients suddenly progresses or changes in transition, we need to be alert to the occurrence of MAS , Its clinical manifestations include changes in fever patterns, hepatosplenomegaly, enlarged lymph nodes, heart, brain and kidney related symptoms, bleeding, thrombosis, and abnormal laboratory tests, such as red blood cell reduction, increased ferritin, and triglycerides Elevate and so on
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Due to the heterogeneity of the disease, the symptoms of each patient may be quite different, so treatment management strategies also vary from person to person
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It is easier to treat and manage patients with mild AOSD, but for moderate to severe patients, regular and timely monitoring is required to understand the disease activity and treatment effect
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The multidisciplinary team plays an important role in the treatment of AOSD patients.
The multidisciplinary team composed of rheumatologists, dermatologists, hematologists, etc.
contributes to the diagnosis of AOSD and the early identification and treatment of complications
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Summary Still’s disease is a highly heterogeneous autoinflammatory disease.
Patients with Still’s disease often have a heavier economic and physical and psychological burden.
Therefore, the diagnosis of the disease is very important to shorten the course of the disease and reduce the burden of the disease.
Play an important role in the treatment of AOSD patients
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