Déficits Immunitaires Primitifs et Cancers : L’Essentiel pour le Praticien

Les déficits immunitaires primitifs (DIP) constituent une famille de pathologies hétérogènes qui s’étoffe au fil du temps. Les connaissances et les découvertes dans le domaine sont perpétuelles. De nouvelles étiologies moléculaires et de nouveaux gènes sont décrits très régulièrement. En 2019, le nombre de gènes reconnus dépasse 430 gènes pour 406 désordres immunitaires [1,2]. Plusieurs classifications phénotypiques et /ou génotypiques se sont succédées, preuve d’un domaine en pleine ébullition. Le phénotype de ces maladies est très variable et l’éventail clinique va de la présentation typique évocatrice, à des tableaux atypiques et déroutants. Il est décrit pour des mutations d’un même gène une variation de l’expression phénotypique [3]. Les manifestations cliniques révélatrices clés peuvent grossièrement se résumer à l’infection, l’auto-immunité, la lymphoprolifération et le cancer. Ces manifestations peuvent être isolées ou associées d’une part, synchrones ou asynchrones d’autre part.L’association cancer et DIP est connue depuis longtemps. La première description date de 1963 [1].Le spectre des DIP qui peuvent prédisposer à un cancer a logiquement suivi les découvertes récentes et plusieurs inconnues sont certainement à déchiffrer. L’amélioration des moyens de diagnostic, les nouvelles thérapeutiques dont la thérapie de substitution et la greffe de cellules souches hématopoïétiques, la meilleure organisation des soins de support, une plus grande maitrise du diagnostic et du traitement curatif des infections opportunistes, l’anticipation des prophylaxies antibiotiques et le meilleur suivi des patients ont permis une amélioration de la survie des DIP, autrefois létaux à un âge précoce. Il en résulte une plus grande probabilité de diagnostiquer des cancers qui n’avaient pas auparavant le temps d’apparaitre : c’est particulièrement le cas des déficits immunitaires combinés sévères (SCID). Le but de cet article est d’attirer l’attention du praticien sur les cancers qui surviennent chez les patients atteints de DIP, surtout qu’ils en constituent la 2ème cause de mortalité après les infections [1]

Macrophage activation syndrome associated with griscelli syndrome type 2: case report and review of literature

Macrophage activation syndrome (MAS) is a severe and potentially fatal life-threatening condition associated with excessive activation and expansion of T cells with macrophages and a high expression of cytokines, resulting in an uncontrolled inflammatory response, with high levels of macrophage colony-stimulating factor and causing multiorgan damage. This syndrome is classified into primary (genetic/familial) or secondary forms to several etiologies, such as infections, neoplasias mainly hemopathies or autoimmune diseases. It is characterised clinically by unremitting high fever, pancytopaenia, hepatosplenomegaly, hepatic dysfunction, encephalopathy, coagulation abnormalities and sharply increased levels of ferritin. The pathognomonic feature of the syndrome is seen on bone marrow examination, which frequently, though not always, reveals numerous morphologically benign macrophages exhibiting haemophagocytic activity. Because MAS can follow a rapidly fatal course, prompt recognition of its clinical and laboratory features and immediate therapeutic intervention are essential. However, it is difficult to distinguish underlying disease flare, infectious complications or medication side effects from MAS. Although, the pathogenesis of MAS is unclear, the hallmark of the syndrome is an uncontrolled activation and proliferation of T lymphocytes and macrophages, leading to massive hypersecretion of pro-inflammatory cytokines. Mutations in cytolytic pathway genes are increasingly being recognised in children who develop MAS in his secondary form. We present here a case of Macrophage activation syndrome associated with Griscelli syndrome type 2 in a 3-years-old boy who had been referred due to severe sepsis with non-remitting high fever, generalized lymphoadenopathy and hepato-splenomegaly. Laboratory data revealed pancytopenia with high concentrations of triglycerides, ferritin and lactic dehydrogenase while the bone marrow revealed numerous morphologically benign macrophages with haemophagocytic activity that comforting the diagnosis of a SAM according to Ravelli and HLH-2004 criteria. Griscelli syndrome (GS) was evoked on; consanguineous family, recurrent infection, very light silvery-gray color of the hair and eyebrows, Light microscopy examination of the hair showed large, irregular clumps of pigments characteristic of GS. The molecular biology showed mutation in RAB27A gene confirming the diagnosis of a Griscelli syndrome type 2. The first-line therapy was based on the parenteral administration of high doses of corticosteroids, associated with immunosuppressive drugs, cyclosporine A and etoposide waiting for bone marrow transplantation (BMT)

Pain Management in Children with Cancer: National Surveys of Practices and Perceptions in Morocco

AIM: The aim of the study was to improve the quality of pain management in Moroccan pediatric oncology units, the Moroccan Society of Paediatric Haematology/Oncology initiated a national quality improvement project in 2014 with the support of the Lalla Salma Foundation for Prevention and Treatment of Cancer. METHODS: To assess the current situation of pain management in Moroccan pediatric oncology patients, two cross-sectional surveys were conducted, involving patient/parental proxies and health-care providers’. RESULTS: The first survey concerned 108 care providers from five institutions. The second survey covered 155 children with cancer from the five Moroccan pediatric oncology units. Among them, 145 reported suffering from pain, which patients/families attributed to the underlying cancer (n = 85), to procedures and treatment (n = 46), or to both the cancer and procedures/treatment (n = 19). Procedural pain was mainly related to lumbar puncture and bone marrow aspirate. The majority of patients/parents reported that pain negatively impacted their emotional, physical, and social functioning. The majority of parents requested further information and communication about pain management. CONCLUSION: Both health-care providers and families of children with cancer in Morocco report need for pain management improvement, including in institutional and educational practices. This current baseline data have informed the development of our ongoing project including continuing education, training, and practice policies development