Monogenic auto-inflammatory diseases associated with actinopathies: A review ofthe literature

P. Mertz a, V. Hentgenb, G. Boursier c, J. Delond, S. Georgin-Laviallee,∗,f

Link to article: https://doi.org/10.1016/j.revmed.2023.06.005

Abstract:

Auto-inflammatory diseases (AIDs) are diseases resulting from an inappropriate activation of innate immunity in the absence of any infection. The field of monogenic AIDs is constantly expanding, with the discovery of new pathologies and pathophysiological mechanisms thanks to pangenomic sequencing. Actinopathies withauto-inflammatorymanifestations are anew emerging group of AIDs, linked to defects in the regulation of the actin cytoskeleton dynamics. These diseases most often begin in the neonatal period and combine to varying degrees a more or less severe primary immune deficiency, cytopenias (especially thrombocytopenia), auto-inflammatory manifestations (especially cutaneous and digestive), atopic and auto-immune manifestations. The diagnosis is to be evoked essentially in front of a cutaneousdigestive auto-inflammation picture of early onset, associated with a primary immune deficiency and thrombocytopenia or a tendency to bleed. Some of these diseases have specificities, including a risk of macrophagic activation syndrome or a tendency to atopy or lymphoproliferation. We propose here a review of the literature on these new diseases, with a proposal for a practical approach according to the main associated biological abnormalities and some clinical particularities. However, the diagnosis remains genetic, and several differential diagnoses must be considered. The pathophysiology of these diseases is not yet fully elucidated, and studies are needed to better clarify the inherent mechanisms that can guide the choice of therapies. In most cases, the severity of the picture indicates allogeneic marrow transplantation.

© 2023 Publié par Elsevier Masson SAS au nom de Société Nationale Française de Médecine Interne (SNFMI).

National Protocol for Diagnosis and Care of Familial Mediterranean Fever

S. Georgin-Laviallea,h,∗, L. Saveya,h, L. Cuissetc, G. Boursiere,h, J.-J. Boffab,h,

M. Delplanquea,h, R. Bourguibaa,h, J.-B. Monfortd,h, I. Touitoue,h, G. Grateaua,h,

I. Kone-Pautf,h, V. Hentgeng,h, Collaborators1

Summary:

Familial Mediterranean Fever is the world's most common monogenic autoinflammatory disease. It mainly affects people from the Mediterranean region. The mutated gene is MEFV, which codes for pyrin. Transmission is autosomal recessive. Patients present with recurrent attacks of fever since childhood, associated with abdominal and/or thoracic pain lasting an average of 2 to 3 days, and a biological inflammatory syndrome. Other symptoms include arthralgia or arthritis of large joints such as the knees and ankles, myalgia of the lower limbs and pseudo-eryzipelas of the ankles. Its most severe complication is inflammatory amyloidosis, or AA amyloidosis, which can lead to renal failure. Treatment is based on colchicine, which helps prevent relapses and the onset of renal amyloidosis.

This work presents national recommendations for the diagnosis, management and follow-up of Familial Mediterranean Fever in France, where we estimate there are between 5,000 and 10,000 patients with the disease at all stages of life. Diagnosis is suspected on the basis of clinical and anamnestic elements, and confirmed by genetic analysis. These recommendations also propose a “treat-to-target” approach to disease treatment, particularly in cases of suspected colchicine resistance - a very rare situation that should remain a situation of elimination, particularly after verification of colchicine compliance. Two special situations are also addressed in these recommendations: renal failure and pregnancy.

​© 2023 Publié par Elsevier Masson SAS au nom de Société Nationale Franc¸ aise de Médecine Interne (SNFMI).

French recommandation for the diagnostic and care of FMF Rev Med int.pdf

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A20 Haploinsufficiency (HA20) is a monogenic autoinflammatory disease associated with an autosomal dominant mutation in the TNFAIP3 gene.: what does the clinician need to know?

I. Elhani a,b,∗, A. Aoubac, Q. Riller d, H. Vergneault e, G. Boursier f,g, F. Rieux-Laucat d, V. Hentgena, S. Georgin-Lavialle b,e,∗

A20 Haploinsufficiency (HA20) is a monogenic autoinflammatory disease associated with an autosomal dominant mutation in the TNFAIP3 gene. It induces a defect in the inactivation of the pro-inflammatory NF-B pathway. Less than 200 cases have been described worldwide. The clinical picture of the disease is essentially based on the association of recurrent fever and/or biologic inflammatory syndrome, aphtosis, often bipolar, and cutaneous folliculitis. However, the clinical spectrum of HA20 is very broad, including gastrointestinal (mainly colonic ulceration), articular, cutaneous, pericardial and lymph node involvement, as well as frequent association with organ-specific or non-specific autoimmune manifestations and/or autoantibodies, including antinuclear antibodies and anti-dsDNA. As a result, the diagnosis of a number of systemic or organic disorders, most notably Behc¸ et’s disease, Crohn’s disease, and sometimes even systemic lupus, has been corrected to HA20 by molecular research for a heterozygous mutation with functional deficiency of TNFAIP3. Although the first signs of the disease often appear in the first years of life, the diagnosis is often made in adulthood and requires the involvement of both paediatric and adult physicians. TreatmentforHA20 isnot codifiedandrelies onconventional or biologicalimmunomodulators and immunosuppressants adapted to the patient’s symptomatology. This review highlights the enormous diagnostic challenges in this autoinflammatory disease.

© 2023 Société Nationale Française de Médecine Interne (SNFMI). Publié par Elsevier Masson SAS. Tous droits réservés.