Still’s Disease in the Constellation of Hyperinflammatory Syndromes: A Link with Kawasaki Disease?
Abstract
:1. Conceptual Evolution of Still’s Disease
2. Conceptual Evolution of Kawasaki Disease
3. Still’s Disease and KD, How Much Are They Related?
Is It Possible to Link Them Clinically?
4. How Their Pathophysiology Could Be Similar?
Innate Immune System Activation
5. How Much Are They Different?
5.1. Clinical Differences
5.2. Adaptive Immune System Induction
5.3. Endothelial Activation
6. Conclusions
7. Take Home Messages
7.1. What Are the Key Elements That Our Analysis Points Out?
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- KD and Still’s disease share a number of clinical and biological similarities but essentially differ from their respective evolutions.
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- Both diseases are underpinned by related physiopathological mechanisms encompassing a potent activation of innate immunity.
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- Rather, they should be considered as belonging to a common clinical spectrum, the extremes of which depend on a variable influence of adaptive immunity.
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- The preferential endothelial activation of KD compared to Still’s disease is strongly enhanced by the release of interleukin 1 alpha and the direct toxicity of the IgA toward the endothelial cells.
7.2. How Might This Impact on Clinical Practice or Future Developments?
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- The deep link between these two syndromes (rather than diseases) implies considering them together to resolve physiopathological or therapeutic research questions.
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- The crucial role of interleukin 1 alpha in inducing cardiac inflammation of KD must be taken into account when choosing targeted biotherapies.
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Clinical Sign | Still’s Disease | Kawasaki Disease |
---|---|---|
Estimated incidence | Children 0.6/<16 years [22] All ethnicities, minor prevalence and incidence variations | Japan: 309–330 cases per 100,000 <5 years [18] Canada (Ontario): 22 cases per 100,000 <5 years [19] Northern Europe: 5.4 to 11.4 cases per 100,000 <5 years [20] |
Age of onset (Peak) | 1–5 years [22] | 2–5 years (1–2 years) |
Male to female ratio | 1/1 | 1.5/1 |
Family clustering | <1% | 1% |
Spiking fever | Yes almost 100% | Yes almost 100% |
Skin rash | Diffuse macular, urticarial (75–80%) | Diffuse Macular, urticarial, scarlatiniform (80%) [23] Oedema and redness of the palms and soles (70%) [23] |
Mucous lesions | Odynophagia (adults 66%) | Conjunctiva redness (89%) [23] Diffuse redness of the oral cavity (72%) [23] Strawberry tongue (56%) [23] Dryness of the lips (85%) [23] |
Adenitis | Diffuse adenitis (42%) | Cervical adenitis (55%) [23] |
Gastro-intestinal symptoms | Abdominal pain | Diarrhoea (60%) [23] |
Hepato-splenomegaly | Children 20% | Hepatomegaly (56%) [23] |
Arthritis | Persistent (25%) | Transient, and unusual |
Heart involvement | Pericarditis (18%) Myocarditis Coronary aneurysms | Pericarditis (18%) [23] Myocarditis (3%) [23] Coronary aneurysms 25% of untreated patients |
Macrophage activation syndrome | Apparent 10% Subclinical 40% | |
Disease course | Monophasic with variable duration (40%) Polycyclic (10%) Persistent (50%) | Monophasic > 97% Recurrent (3%) |
Response to treatment (yes/No) | [24] | |
Corticoids | Yes | Yes |
IV Ig | No | Yes |
Anti TNF | Few | Yes |
Anti IL-1 | Yes | Probably yes, still exploratory |
Anti IL-6 | Yes | Unknown |
Biomarker | Still’s Disease | Kawasaki Disease |
---|---|---|
CRP | Unspecific elevation | Unspecific elevation Very high levels are related to cardiac damage and IVIG resistance |
Complete blood cell count | Polynucleosis, anaemia, and thrombocytosis are indicative of active disease Cytopenia are related to MAS | Polynucleosis, anaemia, and thrombocytosis are indicative of active disease Cytopenia are related to MAS |
↑ d-dimer, ↓ fibrinogen | Indicative of MAS | Indicative of MAS |
LDH, AST, ALT | Associated with disease activity | Associated with disease activity |
Ferritin | Elevated, useful for diagnosis | Variably elevated |
IL-6 | Elevated, may be related with arthritis feature | Very high levels are related to IVIG resistance and coronary aneurysms |
IL-1β | Associated with systemic symptoms | Elevated and related to cardiac damage |
IL-18 | Elevated in active systemic JIA and much higher in MAS | Elevated together with IL1β in active disease |
TNFα | Normal or variably elevated | Elevated in acute phase |
INFγ | Elevated in active systemic JIA and MAS | Very high levels are related to IVIG resistance and coronary aneurysms |
S100 A12 | Elevated in active systemic JIA and MAS | Elevated and corelating with disease activity |
sRAGE * | Decreased during active disease | Decreased during active disease |
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Dusser, P.; Koné-Paut, I. Still’s Disease in the Constellation of Hyperinflammatory Syndromes: A Link with Kawasaki Disease? J. Clin. Med. 2021, 10, 3244. https://doi.org/10.3390/jcm10153244
Dusser P, Koné-Paut I. Still’s Disease in the Constellation of Hyperinflammatory Syndromes: A Link with Kawasaki Disease? Journal of Clinical Medicine. 2021; 10(15):3244. https://doi.org/10.3390/jcm10153244
Chicago/Turabian StyleDusser, Perrine, and Isabelle Koné-Paut. 2021. "Still’s Disease in the Constellation of Hyperinflammatory Syndromes: A Link with Kawasaki Disease?" Journal of Clinical Medicine 10, no. 15: 3244. https://doi.org/10.3390/jcm10153244