Arthropathy with rash, chronic meningitis, eye lesions, and mental retardation

doi:10.1016/S0022-3476(81)80961-4

The Journal of Pediatrics

Volume 99, Issue 1, July 1981, Pages 79-83

https://doi.org/10.1016/S0022-3476(81)80961-4 Get rights and content

Three unrelated children (one girl and two boys) have had since birth a syndrome characterized by a permanent skin rash which becomes more intense during flare-ups associated with fever, lymphadenopathy, splenomegaly, and arthritis symmetrically involving the large joints. In one boy, typical psoriasis was observed at age 3 years. In two patients, roentgenograms of the joints showed early patellar ossification and an abnormal epiphyseal appearance. The three children also had neurologic involvement, with mental retardation, enlarged head circumference, eye lesions, late closure of the anterior fontanel, and a chronic meningitis with infiltration by polymorphonuclear cells. No immunologic abnormalities were found, but polymorphonuclear cells infiltrated the skin, lymph nodes, synovial fluid, and CSF.

References (9)

BrewerEJ et al.
Current proposed revision of JRA criteria
Arthritis Rheum
(1977)
WoodPHN
AnsellBM et al.
Familial anthropathy with rash, uveitis, and mental retardation
Proc R Soc Med
(1975)
BuriotD et al.
Leucémie aigue chez trois enfants atteints d'arthrite chronique juvénile traités par le chlorambucil
Arch Fr Pediatr
(1979)

There are more references available in the full text version of this article.

Cited by (137)

Neutrophilic Urticarial Dermatosis
2024, Dermatologic Clinics
Structure-based Development of Human Interleukin-1β-Specific Antibody That Simultaneously Inhibits Binding to Both IL-1RI and IL-1RAcP
2021, Journal of Molecular Biology
Citation Excerpt :
Except for IL-1RII, IL-1R antagonist (IL-1Ra) is a naturally occurring blocker since it has 30% amino acid sequence homology to IL-1β and provides a negative feedback control of IL-1β signaling pathway.6 Many pathophysiological diseases have been attributed to the derailment of IL-1β regulation, including hereditary autoinflammatory diseases (Muckle-Wells Syndrome7,8 and neonatal-onset multisystem inflammatory disease9 and complex chronic diseases (gout,10,11 type II diabetes mellitus,12–16 amyotrophic lateral sclerosis17–19 and so on). There are two possible mechanisms used in clinical practice for biologics-mediated IL-1β blockade: (1) reagents that block the binding of IL-1β to IL-1RI, and these include anakinra20 and canakinumab21; and (2) antibodies that inhibit the recruitment of IL-1RAcP but not the binding of IL-1β to IL-1RI, and these includes gevokizumab.22
Interleukin-1β (IL-1β) is a potent pleiotropic cytokine playing a central role in protecting cells from microbial pathogen infection or endogenous stress. After it binds to IL-1RI and recruits IL-1 receptor accessory protein (IL-1RAcP), signaling culminates in activation of NF-κB. Many pathophysiological diseases have been attributed to the derailment of IL-1β regulation. Several blocking reagents have been developed based on two mechanisms: blocking the binding of IL-1β to IL-1RI or inhibiting the recruitment of IL-1RAcP to the IL-1β initial complex. In order to simultaneously fulfill these two actions, a human anti-IL-1β neutralizing antibody IgG26 was screened from human genetic phage-display library and furthered structure-optimized to final version, IgG26AW. IgG26AW has a sub-nanomolar binding affinity for human IL-1β. We validated IgG26AW-neutralizing antibodies specific for IL-1β in vivo to prevent human IL-1β-driving IL-6 elevation in C56BL/6 mice. Mice underwent treatments with IgG26AW in A549 and MDA-MB-231 xenograft mouse cancer models have also been observed with tumor shrank and inhibition of tumor metastasis. The region where IgG26 binds to IL-1β also overlaps with the position where IL-1RI and IL-1RAcP bind, as revealed by the 26-Fab/IL-1β complex structure. Meanwhile, SPR experiments showed that IL-1β bound by IgG26AW prevented the further binding of IL-1RI and IL-1RAcP, which confirmed our inference from the result of protein structure. Therefore, the inhibitory mechanism of IgG26AW is to block the assembly of the IL-1β/IL-1RI/IL-1RAcP ternary complex which further inhibits downstream signaling. Based on its high affinity, high neutralizing potency, and novel binding epitope simultaneously occupying both IL-1RI and IL-1RAcP residues that bind to IL-1β, IgG26AW may be a new candidate for treatments of inflammation-related diseases or for complementary treatments of cancers in which the role of IL-1β is critical to pathogenesis.
Involvement of nuclear factor kappa-B in development of neonatal onset multisystem inflammatory disease
2020, Journal of King Saud University - Science
Citation Excerpt :
Epidemiological studies have shown, however, that the prevalence of NOMID in neonates is higher than assumed (Agostini et al., 2004). NOMID is a genetic disorder, which is due to the mutation of auto-inflammatory, these results in multisystem inflammatory disease (Prieur and Griscelli, 1981). NOMID is flattering an important public health concern throughout the world and accounts for premature morbidity and mortality (Prieur et al., 1987).
The present study investigated the relationship between nuclear factor-κB1 gene (NFkB1) and neonatal onset multisystem inflammatory disease (NOMID) among Chinese neonates. We therefore aimed to investigate whether nuclear factor kappa-B involved in development of NOMID among Chinese neonates. Patients with confirm diagnosis of NOMID or healthy neonates was enrolled at Maternal and child health hospital of Hubei province, China. Involvement of poly (ADP-ribose) polymerase-1 (PP-1) and nuclear factor-κB1 was assessed using PCR techniques with the help of DNA sample. A total of 220 Chinese neonates with NOMID, and 220 healthy neonates were completed study. We note that the involvement of del/ins of NFkB1 gene in development of NOMID among Chinese neonates. GG and G SNPs of PP-1 were found responsible for developing NOMID and the individuals with GA SNPs protect responsible for protecting from NOMID. Thus, nuclear factor-κB1 and PP-1 involved in cause of NOMID, and considering as risk of developing is approx. 2 times higher compared to healthy subjects. Our study result shown that polymorphism of nuclear factor-κB1 and PP-1 is involved in development of NOMID in China. Our study suggested that NFkB1 and PP-1 is a possible target for treatment of NOMID; the treatment targeting nuclear NFkB1 and PP-1 is useful for effective patient care. Our study results encourage conducting large trial evaluating role of NFkB1 and PP-1 polymorphism in NOMID.
Cryopyrin-associated periodic syndromes
2018, Revue de Medecine Interne
Les cryopyrinopathies sont associées à des mutations d’un même gène mais regroupent 3 syndromes, par gravité croissante l’urticaire familial au froid, le syndrome de Muckle-Wells et le syndrome chronique, infantile, neurologique, cutané, articulaire (CINCA) également appelé neonatal-onset multisystem inflammatory disease (NOMID). La transmission est le plus souvent autosomique dominante sauf dans le syndrome CINCA/NOMID où prédominent les néomutations. Les mutations du gène codant la cryopyrine, NLRP3, sont à l’origine d’une activité dérégulée de la caspase 1 avec production excessive d’interleukine-1 et un syndrome auto-inflammatoire qui dans l’urticaire familial au froid et le syndrome de Muckle-Wells peut être déclenché ou aggravé par le froid. De plus en plus de mutations sont décrites y compris des mutations somatiques pouvant expliquer des signes survenant à l’âge adulte. Les patients présentent une éruption cutanée pseudo-urticarienne, des arthralgies, des céphalées, parfois de la fièvre, une inflammation biologique mais également dans les formes sévères une atteinte neuro-sensorielle avec surdité de perception, atteinte ophtalmologique et méningite chronique. Certains patients CINCA/NOMID développent de plus une hypertrophie pseudo-tumorale des cartilages de croissance articulaire. L’histoire naturelle de la maladie est en général bénigne dans l’urticaire familial au froid mais sévère dans les autres formes, notamment du fait de l’atteinte neuro-sensorielle. Par ailleurs, un risque d’amylose AA secondaire existe dans toutes les formes en l’absence de contrôle de l’inflammation chronique. Le traitement anti-interleukine-1 par anakinra, rilonacept ou canakinumab permet généralement une rémission complète des symptômes mais des séquelles sont possibles en particulier si se sont déjà développées surdité ou hypertrophie cartilagineuse. Ce traitement est également important pour prévenir l’amylose, à défaut stabiliser ou parfois permettre la régression de lésions constituées.
Cryopyrin-associated periodic syndromes (CAPS) are linked to one single gene mutations, however they are associated with 3 syndromes, which are, from the mildest to the most severe phenotype familial cold urticaria, Muckle-Wells syndrome and chronic, infantile, neurologic, cutaneous, articular (CINCA) syndrome also called neonatal-onset multisystem inflammatory disease (NOMID). Autosomic dominant inheritance is present in most cases but in CINCA/NOMID syndrome where neomutations are more common. Mutations in the gene encoding cryopyrin, NLRP3, are associated with deregulation of caspase-1 activity, excessive interleukin-1 production and an autoinflammatory syndrome, which in familial cold urticaria and Muckle-Wells syndrome may be triggered or worsened by exposure to coldness. More and more mutations are described and even somatic mutations that can explain some clinical signs beginning in adulthood. Patients disclose a pseudo-urticarial rash, arthralgia, headaches, sometimes fever, biological inflammation but also, in severe forms of the disease, neurologic inflammation with central deafness, ophthalmologic inflammation, chronic meningitis. Some CINCA/NOMID patients also develop growth cartilage pseudo-tumoral hypertrophy. Natural disease history is usually benign in familial cold urticarial but severe in the other forms, particularly regarding neuro-sensorial involvement. In addition, secondary AA amyloidosis may develop in all forms in the absence of control of chronic inflammation. Anti-interleukin-1 treatment with anakinra, rilonacept or canakinumab induces in most cases complete remission, however sequelae may be present, particularly if central deafness or cartilage bone hypertrophy have already developed. This treatment is also important to prevent secondary amyloidosis or stabilize and even sometimes allow improvement of amyloidosis lesions.
When to Suspect Autoinflammatory/Recurrent Fever Syndromes
2017, Pediatric Clinics of North America
Citation Excerpt :
Unlike cold urticaria, localized cold challenge (ie, ice cube test) will not precipitate an attack in FCAS, because full-body cold exposure is necessary. NOMID is the most severe variant of CAPS, with patients exhibiting rash at or shortly after birth, aseptic meningitis, cerebral atrophy, uveitis, and hearing loss and mental retardation.49–51 The chronic arthropathy in NOMID is severe and deforming due to recurrent bouts of inflammation leading to epiphyseal and patellar overgrowth.
Periodic Fever Syndromes and Other Inherited Autoinflammatory Diseases
2015, Textbook of Pediatric Rheumatology

View all citing articles on Scopus

¹: Supported by INSERM CRL 79-5.232.4

View full text

Original articleArthropathy with rash, chronic meningitis, eye lesions, and mental retardation1

Current proposed revision of JRA criteria

Arthritis Rheum

Familial anthropathy with rash, uveitis, and mental retardation

Proc R Soc Med

Leucémie aigue chez trois enfants atteints d'arthrite chronique juvénile traités par le chlorambucil

Arch Fr Pediatr

Original article
Arthropathy with rash, chronic meningitis, eye lesions, and mental retardation1