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Yimaitong edited and sorted, please do not reprint
without authorization.
Autoinflammatory diseases are diseases of the innate immune system, including monogenic and polygenic disorders
.
The literature suggests that rare polygenic autoinflammatory diseases have different clinical features and are challenging
to diagnose due to the combination of multiple nonspecific manifestations.
In addition, due to its complex etiology, the pathogenesis remains unclear
.
This review will review recent advances in the clinical manifestations, diagnosis, and treatment of polygenic autoinflammatory diseases1, including Schnitzler syndrome, adult Still's disease (AOSD), SAPHO syndrome (synovitis,
Schnitzler syndrome
Schnitzler syndrome is a rare acquired autoinflammatory disorder characterized by
.
The Strasbourg Standard 2, revised in 2014, is most commonly used (Table 1).
Table 1 Diagnostic criteria for Schnitzler syndrome
In the treatment of Schnitzler syndrome, nonsteroidal anti-inflammatory drugs (NSAIDs) and immunosuppressants are less effective
.
Interleukin(IL)-1 receptor antagonists have been shown to be effective
.
The results of the case report showed that fever, arthritis, and skin lesions in patients with Schnitzler syndrome disappeared and clinical symptoms improved
after treatment with the IL-1 receptor antagonist anakinra.
In addition, studies have shown that both rilonacept and canakinumab are effective
in the treatment of patients with Schnitzler syndrome.
Steele disease in adults
AOSD is a rare systemic inflammatory disorder characterized by fever (typically flaccid fever in the hot form), arthralgias and/or arthritis, rash (often associated with fever, typically orange-red macules or maculopapular rashes), and hyperferritinemia, lymphadenopathy, and leukocytosis
.
Diagnosis is mainly based on clinical presentation and excludes infectious diseases, malignancies, and other rheumatic diseases, with Yamaguchi criteria, Cush criteria 3, and Faterel criteria (Table 2).
Table 2 Diagnostic criteria for adult Still's disease
NSAIDs, disease-modifying antirheumatic drugs (DMARDs), and glucocorticoids are the usual treatment
for AOSD.
The IL-6 inhibitor
in refractory cases.
In addition, the patient's response to treatment depends primarily on the disease phenotype, such as response to tocilizumab for arthritis and chronic arthritis phenotypes, and response to anakinra for systemic and non-arthritic phenotypes, suggesting that AOSD treatment may be adjusted
depending on the patient's clinical presentation.
Canakinumab has been approved by the U.
S.
Food and Drug Administration (FDA) and the European Medicines Quality Agency for the treatment of AOSD and systemic
Available data suggest that canakinumab is effective and well tolerated in the treatment of AOSD
.
SAPHO syndrome/CRMO/CNO
SAPHO syndrome/CRMO/CNO is a rare condition with chronic osteoarthropathy and cutaneous manifestations that can affect the skeletal system
including the anterior chest wall, long bones, and spine.
SAPHO syndrome often occurs in adults and presents with aseptic arthritis (synovitis), cutaneous manifestations such as severe acne and
.
CRMO/CNO primarily affects children, and the clinical presentation is heterogeneous, which can present with swelling, severe bone pain, fever, malaise, and weight loss in the affected area, and symptoms associated with bone inflammation and pain usually worsen
at night.
The diagnosis of SAPHO/CRMO/CNO is based on clinical presentation and imaging features
.
The most commonly used diagnostic criterion for SAPHO syndrome is criterion 4 developed by Benhamou and colleagues
.
The diagnosis of CRMO/CNO is confirmed by the exclusion of differential diagnoses such as bacterial osteomyelitis and malignancy
.
Table 3 Diagnostic criteria for SAPHO syndrome
Conventional treatment for SAPHO syndrome/CRMO/CNO includes NSAIDs, DMARDs, glucocorticoids, bisphosphonates, and antibiotics
.
Patients refractory to NSAIDs and DMARDs are commonly treated with TNF inhibitors, such as methotrexate, usually with
.
IL inhibitors such as tocilizumab, anakinra, canakinumab,
in the treatment of patients with SAPHO syndrome/CRMO/CNO.
In addition, the CNO/CRMO subgroup of the Pediatric Arthritis and Rheumatology Research Consortium (CARA) developed a standardized regimen for CNO/CRMO and developed three treatment consensus regimens for children refractory to NSAIDs: sulfasalazine or methotrexate, TNF inhibitors with or without methotrexate, and bisphosphonates
.
Behcet's disease
BD is a multi-systemic, unexplained autoinflammatory disease, mainly manifested as recurrent oral ulcers, genital ulcers, uveitis and skin lesions, can also involve joints, nervous system, gastrointestinal tract and other organs, and can also affect large and small blood vessels to cause idiopathic systemic
.
The diagnosis of BD is challenging
due to the lack of specificity of the clinical presentation.
The 2014 International Research Group on Behcet's Disease (ICBD) from 27 countries is widely used clinically, with an overall score of ≥ 4 to diagnose BD5 (Table 4).
Table 4 Behcet's disease scoring system
NSAIDs, DMARDs, and glucocorticoids are the usual treatment for
Behcet's disease.
Higher doses of glucocorticoids are effective in treating patients with acute exacerbations of BD with vascular involvement, neurobehcet's disease (NBD), and refractory or severe gastrointestinal involvement
.
Oral and genital ulcers should be treated
with topical corticosteroids.
In Japan, aprumistel is approved for the treatment of recurrent canker sores
.
In addition, studies have shown that
.
Emerging evidence suggests that anti-TNF-α therapy is effective in patients with refractory, severe BD, particularly ocular, central nervous system, and gastrointestinal involvement, such as infliximab and adalimumab
.
Analkinin and Canakinumab have been shown to be effective in the treatment of Behcet's disease-associated uveitis and significantly reduce the onset of
eye inflammation.
against BD.
NOD2-related autoinflammatory diseases
Formerly known as nucleotide-binding oligomerizing domain protein 2 (NOD2)-associated autoinflammatory disease, YAOS has clinical features associated with
specific variants of the NOD2 sequence.
Patients may present with recurrent fever lasting days to weeks, erythema or plaque, and gastrointestinal symptoms
such as mild to moderate abdominal pain, bloating,
The disease can lead to chronic pain syndrome and disability, but rarely affects internal organs
.
Its diagnosis depends mainly on clinical phenotype and genotypic characteristics (Table 5).
Table 5 Diagnostic criteria for NOD2-related autoinflammatory diseases
First-line treatment of YAOS includes glucocorticoids and/or sulfasalazine
.
Corticosteroids have been shown to reduce disease severity and duration of flare-ups, and sulfasalazine therapy can significantly improve symptoms
.
In one retrospective study, tocilizumab improved symptoms and physical function
in adults with YAOS.
Canakinumab has also been shown to be effective and well tolerated
.
PFAPA syndrome
PFAPA syndrome is the most common autoinflammatory disease in children and the most common cause of periodic fever in children, with delayed onset
in adulthood.
Its clinical features are predominantly recurrent fever, which can last about 3 to 6 days and occur every 3 to 8 weeks
.
Other features include pharyngitis, stomatitis, cervicitis, and leukocytosis
.
PFAPA syndrome in adults presents similarly, with recurrent fever with erythematous pharyngitis most relevant
to the diagnosis.
The diagnosis of PFAPA syndrome is based primarily on the following clinical criteria, as well as the exclusionary diagnosis6 (Table 6).
Table 6 Diagnostic criteria for PFAPA syndrome
PFAPA syndrome can be prevented with colchicine
.
Tonsillectomy is effective in children with PFAPA syndrome but not in adults
.
in both children and adults.
Corticosteroids
are often used at the onset of illness.
In addition, studies have shown that patients with the IL-1 inhibitors anakinra and canakinumab have a rapid clinical response
.
conclusion
Schnitzler syndrome, AOSD, SAPHO syndrome/CRMO/CNO, BD, YAOS, and PFAPA syndromes are a rare group of polygenic autoinflammatory diseases that exhibit different clinical features and are extremely challenging to diagnose, and further research is needed to understand the pathogenesis
of these diseases 。 In terms of treatment, despite the widespread clinical use of conventional therapeutic drugs, biologics targeting inflammatory cytokines (including IL-1, IL-6, TNF-α, IL-17A, and IL-18) have been shown to improve the symptoms and signs of polygenic autoinflammatory diseases, and biologics have shown good efficacy
.
References:
1.
Efthimiou P, Petryna O, Nakasato P, Kontzias A.
New insights on multigenic autoinflammatory diseases[J].
Ther Adv Musculoskelet Dis.
2022 Sep 3; 14:1759720X221117880.
doi: 10.
1177/1759720X221117880.
PMID: 36081748; PMCID: PMC9445512.
2.
ZHANG
Diagnosis and treatment of Schnitzler syndrome[J].
Chinese Journal of Hematology, 2018, 39(12):1052-1056.
3.
Guidelines for the diagnosis and treatment of Still's disease in adults[J].
Chinese Journal of Rheumatology, 2010(07):487-489.
4.
SHI Suyu, LIU Xiaohong, SONG Laitao, YANG Hui, ZHANG Qianqian.
Research progress of SAPHO syndrome[J].
Chinese Journal of Orthopaedic Surgery, 2020, 28(19):1783-1787.
5.
Zheng Wenjie, Zhang Na, Zhu Xiaochun, Chi Shuhong, Zhang Wen, Wei Wei, Zhao Yan, Dong Yi.
Diagnosis and treatment of
Chinese Journal of Internal Medicine, 2021, 60(10):860-867.
6.
YU Tingting, LIANG Weiling, LIU Chenjing, WU Qian, CHEN Guanrong, LIU Yulong, ZHAO Xiaodong, MAO Huawei.
Analysis of 17 cases of periodic fever syndrome in children[J].
Journal of Chongqing Medical University, 2020, 45(08):1178-1183.
DOI: 10.
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