Break down the barriers of auto-inflammation:How to deal with a monogenic auto-inflammatorydisease and immuno-haematological features in 2022?

First author : Hélène Vergneault

Review: Immunology

Link to article: DOI: 10.1111/imm.13579

Principales caractéristiques immuno-hématologiques en fonction du principal mécanisme physiopathologique impliqué.

Abstract:

In the past few years, the spectrum of monogenic systemic auto-inflammatory diseases (MSAID) has widely expanded beyond the typical recurrent fever. Immunohaematological features, as cytopenias, hypogammaglobulinemia, hypereosinophilia,lymphoproliferation and immunodeficiency, have been described in association of several MSAID. The objective of this review was to describe these particular MSAID. MSAID must be suspected in front of immuno-haematological features associated with non-infectious recurrent fever, chronic systemic inflammation, inflammatory cutaneous manifestations, arthritis or inflammatory bowel disease. Genes and cellular mechanisms involved are various but some of them are of special interest. Defects in actine regulation pathway are notably associated with cytopenia and immune deficiency. Because of their frequency, ADA2 deficiency and Vacuoles, E1-Enzyme, X-linked, auto-inflammatory, Somatic (VEXAS) syndrome deserve to be noticed. ADA2 deficiency results in polyarteritis nodosalike presentation with a wide panel of manifestations including cytopenia(s), lymphoproliferation and immune deficiency. Neutrophilic dermatosis or chondritis associated with macrocytic anaemia or myelodysplasia should lead to screen for VEXAS. Of note, most of MSAID are associated with inflammatory anaemia. We proposed here a clinical and pragmatic approach of MSAID associated with immuno-haematological features.

Vergneault - Break down the barriers of auto‐inflammation How to deal with a monogenic AI.

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Characteristics of familial Mediterranean fever after 65 years of age

First author: François Rodrigues et al.

Link to article: https://doi.org/10.1016/j.ejim.2024.10.010

              Familial Mediterranean Fever (FMF) is an autosomal recessive disease caused by mutations in MEFV, characterized by recurrent febrile attacks. The natural history of the disease, which began in children and had a high mortality rate in the last century, is unknown in people over 65.

        This retrospective study included the records of 59 patients with FMF followed at Hôpital Tenon (Paris, France), representing 9% of the total number of patients followed for FMF. The median age was 73 years. Although all patients were treated with colchicine, the study population, born in the 1940s-1950s, had a late diagnosis (median age 28 years) and a delayed initiation of colchicine (35 years, median year of introduction 1980). 73% of patients had an elevated intercritical CRP on colchicine, and 37% had to receive an inteleukin-1 inhibitor, with good tolerability. The prevalence of AA amyloidosis was 10%. The most frequent comorbidities were cardiovascular (59% of patients) and, unexpectedly, hepatic (37%), with a high frequency of non-alcoholic, non-viral cirrhosis (27%) and no associated diabetes, suggesting a link with FMF. Nine patients (15%) had died at the time of collection, two from complications of FMF, two from hepatic cirrhosis, and five from infections.

             In conclusion, the study indicates that FMF can remain active after the age of 65, motivating specialized lifelong follow-up with CRP monitoring between attacks, as well as the prescription of biotherapy in the event of unsatisfactory disease control.

Caractéristiques de la fièvre méditerranéenne familiale après 65 ans.pdf

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Provisional diagnostic criteria for systemic inflammatory trunk recurrent acute macular eruption diagnosis (SITRAME)

First author: Angèle Soria

Link to article: https://pubmed.ncbi.nlm.nih.gov/36426626/

Summary:

The Systemic Inflammatory Trunk Recurrent Acute Macular Eruption (SITRAME) syndrome is a recently described sporadic autoinflammatory syndrome in adults. It is characterized by recurrent non-pruritic macular eruptions on the trunk, accompanied by at least one documented episode of systemic inflammation with elevated C-reactive protein (CRP) levels during flares. The eruptions have a fixed topography and appear rapidly with confluent exanthem. They always involve at least the trunk, sparing certain areas of the skin with clear demarcation. The median duration of the eruptions was 3 days (range: 2–7 days).

No specific genetic mutation has been associated with the SITRAME syndrome. The objective of this study was to define diagnostic criteria to improve its identification. Four major criteria were defined as being present in all the patients studied: systemic inflammation with CRP > 5 mg/mL during a skin flare, non-pruritic macular trunk eruption, recurrence with at least three different episodes, and acute flares lasting less than 8 days. All four major criteria are mandatory for the diagnosis of SITRAME. Four minor criteria were present in at least half of the patients. At least one minor criterion is required for the diagnosis. Additionally, exclusion criteria include another monogenic autoinflammatory disease, an evolving neoplasm, or an autoimmune disease.

Histopathological evaluation showed limited specificity, characterized by a markedly poor dermal infiltrate, mainly with lymphocytes and minimal spongiosis. This shows that skin biopsy is not a discriminating diagnostic criterion. When comparing the major criteria of SITRAME with those of other adult-onset autoinflammatory syndromes, such as Schnitzler's syndrome and adult-onset Still's disease, none of the CAPS or adult-onset Still's disease patients met the major criteria for SITRAME.

The diagnosis of SITRAME syndrome requires the presence of four mandatory major criteria, at least one minor criterion, and the exclusion criteria.

Provisional diagnostic criteria for systemic inflammatory trunk recurrent acute.pdf

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