Chronic Recurrent Multifocal Osteomyelitis Involving the Mandible – A Rare Case Report

Chronic recurrent multifocal osteomyelitis (CRMO) is an uncommon, aseptic, autoinflammatory condition characterized by multifocal bone lesions with pain, swelling, and frequent exacerbations and remissions. It is noteworthy that these lesions occur without any identifiable etiology or microbiologic finding. The clavicle and metaphyses of the long bones are often involved whereas involvement of the mandible is considered rare. It is usually diagnosed by exclusion of other diseases. As it shares most of its features with the more commonly occurring infective osteomyelitis, patients are often unnecessarily subjected to prolonged courses of antibiotics, serial radiation exposures, and repeated bone biopsies. We present a case of CRMO involving the mandible. Our primary objective is to demonstrate the clinical features of this uncommon disorder, highlighting the radiographic appearance. Familiarity with this condition among radiologists greatly increases the likelihood for early diagnosis and formulating an appropriate treatment plan.

UBA1 and DNMT3A Mutations in VEXAS Syndrome. A Case Report and Literature Review

VEXAS syndrome is a recently described X-linked autoinflammatory condition associated with somatic mutation of the UBA1 gene. It often coexists with MDS which can occur due to DNMT3A mutation. These patients, predominantly males, present after the fifth decade of life with unique systemic inflammatory clinical features and have hematological abnormalities and vacuolated precursor cells on bone marrow pathology. Here we describe a unique case of VEXAS syndrome in a patient harboring DNMT3A gene mutation with coexisting UBA1 mutation with a review of literature.

Behçet’s Disease—Do Microbiomes and Genetics Collaborate in Pathogenesis?

Behçet’s disease (BD) is a multisystem autoinflammatory condition characterized by mucosal ulceration, breakdown of immune privilege sites and vasculitis. A genetic basis for BD has been described in genome-wide and validation studies. Similarly, dysbiosis of oral and gut microbiomes have been associated with BD. This review will describe links between genetic polymorphisms in genes encoding molecules involved in gut biology and changes seen in microbiome studies. A potential decrease in bacterial species producing short chain fatty acids linked to mutations in genes involved in their production suggests a potential therapy for BD.

The VEXAS Syndrome: Uncontrolled Inflammation and Macrocytic Anaemia in a 77-Year-Old Male Patient

The VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently described X-linked autoinflammatory condition caused by a somatic mutation of the UBA1 gene and characterized by an evolving phenotype. This includes inflammatory processes such as recurrent fever, Sweet’s syndrome of the skin, pulmonary fibrosis, relapsing polychondritis and venous thromboembolism. An important feature, present in almost all cases, is the development of a macrocytic anaemia with vacuolization of myeloid and erythroid precursors. Usually, these patients require high doses of steroids to control symptoms and respond poorly to disease-modifying drugs. We describe a new case of the VEXAS syndrome presenting with Sweet’s syndrome which has now been followed for 6 years.

Pfeifer-Weber-Christian Disease and Benign Multiple Subcutaneous Noninfiltrative Angiolipomas: A Puzzling Case and Review of a Rare Entitety

Background: Pfeifer-Weber-Christian disease (PWCD) is one of many rare diseases that may be easily missed if there is not a high degree of suspicion. Angiolipomas are rare, benign subcutaneous tumors, composed of adipose tissue and blood vessels and often containing fibrin thrombi. The majority of angiolipomas occur sporadically; however, there is a minority of cases that have been associated with long-term corticosteroid use. Case presentation: We report here an unusual case of PWCD associated with benign multiple subcutaneous noninfiltrative angiolipomas confirmed by skin biopsy. Systemic corticosteroid therapy was not effective at reducing flares of panniculitis, and during this therapy angiolipomas gradually increased in size. In contrast, administration of oral Cyclosporine A (CyA) led to a rapid remission of the PWCD. Conclusions: As PWCD has no known aetiology and no specific treatment has been established, the successful therapy with the CyA supports the hypothesis that PWCD is a T cell mediated autoinflammatory condition. Also, this case represent very rare side effects of corticosteroid therapy, such as induction of de novo angiolipomas or increased growth of existing tumours. This case bring diagnostic difficulties in everyday clinical practice, especially in patients with panniculitides, but histopathological evaluation usually resolves the dilemma.

A novel disorder involving dyshematopoiesis, inflammation, and HLH due to aberrant CDC42 function

Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation due to inadequate restraint of overactivated immune cells and is associated with a variable clinical spectrum having overlap with more common pathophysiologies. HLH is difficult to diagnose and can be part of inflammatory syndromes. Here, we identify a novel hematological/autoinflammatory condition (NOCARH syndrome) in four unrelated patients with superimposable features, including neonatal-onset cytopenia with dyshematopoiesis, autoinflammation, rash, and HLH. Patients shared the same de novo CDC42 mutation (Chr1:22417990C>T, p.R186C) and altered hematopoietic compartment, immune dysregulation, and inflammation. CDC42 mutations had been associated with syndromic neurodevelopmental disorders. In vitro and in vivo assays documented unique effects of p.R186C on CDC42 localization and function, correlating with the distinctiveness of the trait. Emapalumab was critical to the survival of one patient, who underwent successful bone marrow transplantation. Early recognition of the disorder and establishment of treatment followed by bone marrow transplant are important to survival.