Phenotypic Variability in PRKCD: a Review of the Literature.

PURPOSE: Protein kinase C δ (PKCδ) deficiency is a rare genetic disorder identified as a monogenic cause of systemic lupus erythematosus in 2013. Since the first cases were described, the phenotype has expanded to include children presenting with autoimmune lymphoproliferative syndrome-related syndromes and infection susceptibility similar to chronic granulomatous disease or combined immunodeficiency. We review the current published data regarding the pathophysiology, clinical presentation, investigation and management of PKCδ deficiency. METHODS: Literature review was performed using MEDLINE. RESULTS: Twenty cases have been described in the literature with significant heterogeneity. CONCLUSION: The variation in clinical presentation delineates the broad and critical role of PKCδ in immune tolerance and effector functions against pathogens.

Navigating chronic pain: how taking a few wrong turns can miss sinister pathology.

Bone sarcomas are rare in childhood, and their presentation can often mimic more benign complaints or chronic musculoskeletal pain. Ewing sarcomas in particular are often diagnosed after a significant delay from the onset of symptoms. At a population level, a long diagnostic delay is not necessarily associated with worse survival , as tumours that display slow growth also tend to be less aggressive. For any specific individual however, a delayed diagnosis can result in a larger tumour that is more difficult to treat. We explore a case of Ewing sarcoma and discuss how the presenting features, approach to imaging and the role of clinician cognitive bias may have led to diagnostic delay.Ewing sarcoma is treated with chemotherapy and surgery and/or radiotherapy based on the initial site of disease, size of tumour and response to initial treatment. With current UK treatments, overall survival is approximately 70% for localised tumours and up to 20% in those with metastatic disease. Bone sarcomas usually present with deep-seated mechanical bone pain akin to toothache. The pain can be intermittent over the course of days or weeks, but pain occurring at night should be considered a red flag. Swelling may also present. On plain X-ray, bone sarcomas can demonstrate areas of bone destruction, new bone formation, periosteal inflammation and soft tissue swelling, but in some cases the changes are very subtle. Persistent unexplained symptoms require MRI to exclude tumours and detect potential benign causes that are amenable to treatment.