A case series of ten plus one deficiency of adenosine deaminase 2 (DADA2) patients in Iran.

BACKGROUND: Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disease caused by mutations in the ADA2 gene. DADA2 has a broad spectrum of clinical presentations. Apart from systemic manifestations, we can categorize most of the signs and symptoms of DADA2 into the three groups of vasculitis, hematologic abnormalities, and immunologic dysregulations. The most dominant vasculitis features are skin manifestations, mostly in the form of livedo racemosa/reticularis, and early onset ischemic or hemorrhagic strokes. Hypogammaglobulinemia that is found in many cases of DADA2 brings immunodeficiencies into the differential diagnosis. Cytopenia, pure red cell aplasia (PRCA), and bone marrow failure (BMF) are the hematologic abnormalities commonly found in DADA. CASE PRESENTATION: We introduce eleven patients with DADA2 diagnosis, including two brothers and sisters, one set of twin sisters, and one father and his daughter and son. Ten patients (91%) had consanguineous parents. All the patients manifested livedo racemose/reticularis. Ten patients (91%) reported febrile episodes, and seven (64%) had experienced strokes. Only one patient had hypertension. Two of the patients (11%) presented decreased immunoglobulin levels. One of the patients presented with PRCA. Except for the PRCA patient with G321E mutation, all of our patients delivered G47R mutation, the most common mutation in DADA2 patients. Except for one patient who unfortunately passed away before the diagnosis was made and proper treatment was initiated, the other patients' symptoms are currently controlled; two of the patients presented with mild symptoms and are now being treated with colchicine, and the eight others responded well to anti-TNFs. The PRCA patient still suffers from hematologic abnormalities and is a candidate for a bone marrow transplant. CONCLUSIONS: Considering the manifestations and the differential diagnoses, DADA2 is not merely a rheumatologic disease, and introducing this disease to hematologists, neurologists, and immunologists is mandatory to initiate prompt and proper treatment. The efficacy of anti-TNFs in resolving the symptoms of DADA2 patients have been proven, but not for those with hematologic manifestations. Similarly, they were effective in controlling the symptoms of our cohort of patients, except for the one patient with cytopenia.

The role of inflammatory mediators in the pathogenesis of periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome.

INTRODUCTION: As a recurrent disease, periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is characterized by episodes of febrile attacks and is often prominent in children under five years of age. However, the etiology of this condition has not been fully understood yet. MATERIALS AND METHODS: The search in the extensive literature of peer-reviewed articles published from the inception to December 2021 was conducted to identify the relevant studies, using the electronic databases of MEDLINE/PubMed, Embase, Scopus, the Cochrane Library, and the Web of Science. RESULTS: The analysis of complex relationships indicates that inflammatory factors, such as various cytokines and acute-phase proteins (APPs), play leading roles in the pathogenesis of this disease. Accordingly, this article summarizes the current state of knowledge to explain the mechanisms involved in inflammatory responses among patients with PFAPA syndrome and investigate its role in the pathogenesis of this disease. Moreover, the possibilities for further implementation of new therapeutic strategies are pointed out. CONCLUSION: It is concluded that some pathophysiological processes are associated with immune dysregulation, which itself may be secondary to environmental factors, genetic background, and underlying diseases, including latent infections that multiply inflammatory mediators. elevated inflammatory markers similarly play a significant part in the clinical outcomes of this condition, whose pyrogenic nature is the reason for the development of episodes of febrile attacks in the population of patients suffering from PFAPA syndrome.

Surgical complications of endoscopic approach to skull base: analysis of 584 consecutive patients.

PURPOSE: Endoscopic techniques have been widely applied for challenging cranial base surgeries in recent years. In this study, we evaluated the safety and efficacy of using the endoscopic endo-nasal route for various skull base pathologies in terms of postoperative complications. METHODS: A total of 584 consecutive patients who underwent endoscopic skull base surgery were studied. Peri- and post-operative complications and risk factors affecting the occurrence of these complications were evaluated. RESULTS: 648 endoscopic skull base surgical procedures were performed on 584 patients (47.8% females and 52.2% males) with the mean age of 41.2 years. Pituitary adenoma (69.3%) was the most common pathology. Post-operative mortality was 2.0%. The rates of post-operative permanent neurological deficit (one case of 6th nerve injury, two 12th nerve injuries and one hemiparesis) and visual deterioration were 0.6% and 1.5%, respectively. Ten patients (1.7%) were complicated with meningitis and it was the cause of death in 3. Systemic complications not directly attributable to skull base surgical access occurred in 2% (11 patients) with 5 mortalities. The rate of intra-operative vascular injury was 1% and among them one patient died due to PCA injury. The most common post-operative complications were diabetes insipidus (12.5%), anterior pituitary dysfunction (10.6%) and CSF leak (3.6%), respectively. In general, reoperation, malignant lesions, and level IV of surgical complexity were associated with a higher incidence of complications. CONCLUSION: Endoscopic endo-nasal approach can be a safe and less-morbid first-line treatment of patients with various skull base lesions.