Evaluation of human coronavirus OC43 and SARS-COV-2 in children with respiratory tract infection during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic is an overwhelming crisis across the world. Human Coronavirus OC43 (HCoV-OC43) is a Betacoronavirus responsible mostly for mild respiratory symptoms. Since the presentations of HCoV-OC43 and severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) are believed to resemble a lot, the aim of this study was to evaluate the frequency and characteristics of HCoV-OC43 in the current pandemic and the rate of coinfection for the two viruses. One hundred and seventeen patients referred to Children's Medical Center, Tehran, Iran with respiratory symptoms were included. Real-time reverse transcription-polymerase chain reaction (RT-PCR) methods were performed for the detection of HCoV-OC43 and SARS-COV-2. Totally, 23 (20%) had a positive RT-PCR for HCoV-OC43 and 25 (21%) were positive for SARS-COV-2. Two patients (2%) had a positive PCR for both HCoV-OC43 and SARS-COV-2. The two groups showed significant differences in having contact with family members with suspected or confirmed COVID-19 (p = 0.017), fever (p = 0.02), edema (p = 0.036), vomiting (p < 0.001), abdominal complaints (p = 0.005), and myalgia (p = 0.02). The median level of lymphocyte count in patients with HCoV-OC43 was significantly lower than patients with SARS-COV-2 infection (p = 0.039). The same frequency of SARS-COV-2 and HCoV-OC43 was found in children with respiratory symptoms during the COVID-19 pandemic. The rate of coinfection of SARS-COV-2 with HCoV-OC43 in our study was 0.08. Further research into the cocirculation of endemic coronaviruses, such as HCoV-OC43 and SARS-CoV2, in different regions, is highly recommended. Attempts to determine the geographic distribution and recruit more flexible test panel designs are also highly recommended.

Wolman disease presenting with hemophagocytic lymphohistiocytosis syndrome and a novel LIPA gene variant: a case report and review of the literature.

BACKGROUND: Wolman disease is a rare disease caused by the absence of functional liposomal acid lipase due to mutations in LIPA gene. It presents with organomegaly, malabsorption, and adrenal calcifications. The presentations can resemble hemophagocytic lymphohistiocytosis, the life threatening hyperinflammatory disorder. Since the disease is very rare, clinicians might not think of it when a patient presents with hemophagocytic lymphohistiocytosis, and the opportunity to treat it properly can be lost, thus leading to demise of the child. CASE PRESENTATION: We present a 4.5-month-old Caucasian boy with fever, icterus, and hepatosplenomegaly who was treated according to presumed hemophagocytic lymphohistiocytosis disease. Wolman disease was diagnosed after the death of the child. There are some case reports in the literature presenting patients with Wolman disease primarily diagnosed as hemophagocytic lymphohistiocytosis, which we discuss in this review. The genetic analysis revealed after his demise was compatible with Wolman disease, introducing a novel mutation in LIPA gene: exon 4: NM_001127605: c. G353A (p.G118D), which converts the glycine amino acid to aspartic acid. CONCLUSIONS: Considering the similarities in presentation of Wolman disease and hemophagocytic lymphohistiocytosis, the patient's life can be saved if special attention is paid to presenting features of a patient with suspected hemophagocytic lymphohistiocytosis, that is special attention to symptoms, findings on physical exams, laboratory values, and radiologic findings, and the proper treatment is urgently initiated. Reporting the novel mutations of Wolman disease can help geneticists interpret the results of their patients' genetic studies appropriately, leading to correct diagnosis and treatment.

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.

Colchicine versus cimetidine: the better choice for Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome prophylaxis, and the role of MEFV gene mutations.

BACKGROUND: During childhood, the most common periodic fever is periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome. The effective treatment and prevention of febrile attacks improve these patients' and their families' quality of life. However, there is no single strategy or evidence-based guideline to manage this syndrome, and most of them are based on consensus treatment plans. METHODS: This randomized controlled trial was carried out on 67 PFAPA patients referred to three tertiary centers of pediatric rheumatology. The patients were divided into two groups, including group 1 (n = 36) receiving prednisolone plus colchicine and group 2 (n = 31) receiving prednisolone plus cimetidine. Demographic characteristics and the number of febrile episodes were compared between the two groups before and after the intervention. RESULTS: In both groups, the number of febrile episodes after the treatment decreased (P ≤ 0.001). Statistical Analysis showed no significant difference between the two groups (P = 0.88). Moreover, 44 patients from both groups were checked for the MEFV gene. There were no statistical differences between MEFV positive and negative subgroups in response to colchicine (P = 1). CONCLUSION: This study showed that both drug regimens are significantly effective in preventing febrile attacks in PFAPA syndrome, and the presence of a MEFV gene mutation might not be the only significant risk factor for a response to colchicine. TRIAL REGISTRATION: IRCT, IRCT20191222045847N1. Registered 23 October 2019, https://fa.irct.ir/search/result?query=IRCT20191222045847N1.

PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and adenitis) syndrome: an overview of genetic background.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an autoinflammatory disorder with an uncertain origin. PFAPA manifestations occur in the form of regular attacks accompanied by a rise in inflammatory markers. Regarding the family clustering of PFAPA and its similarities with other autoinflammatory disorders such as familial Mediterranean fever, a genetic basis is suggested for the disease. Studies have conducted genome analysis in order to find possible gene variants in PFAPA. Associations with variations in several genes such as MEFV, NLRP, TNFRSF1A, CARD15/NOD2, and MVK have been suggested and analyzed. Inflammasomes, intracellular proteins that are members of innate immunity and activate interleukin-1b (IL-1b) and IL-18, are proposed to be involved in PFAPA pathogenesis. The investigations show that a single gene cannot be found in association with PFAPA, and that it might have a multifactorial or polygenic basis, in which an environmental trigger can provoke inflammasome activation and activate PFAPA flares.

Post-photorefractive Keratectomy Pain and Corneal Sub-basal Nerve Density.

PURPOSE: The perceived and reported pain of patients receiving photorefractive keratectomy (PRK) widely varies. We assessed the potential role of the subbasal nerve plexus density as a predictor of postoperative pain level. Consecutive patients scheduled to undergo PRK at the Refractive Surgery Clinic of Farabi Eye Hospital, Tehran, were approached. METHODS: Forty-nine myopic left eyes from 49 patients who consented to undergo scanning slit confocal microscopy assessments preoperatively were included. ImageJ (1.48v) was used to measure the captured subbasal nerve length. Postoperative pain intensity was assessed by the Visual Analog Scale (VAS) (score range: 0 for no pain to 10 for the maximum possible) on the next day of surgery. RESULTS: The mean age of the patients was 27.55 (range: 19-40) years. The median reported pain level was 5. Approximately 32.7% of the subjects reported a pain score of 6 or higher. Mean nerve density was 19.54 (range: 14.34-24.73) mm/mm2. Nerve density was not correlated with the reported intensity of pain (P = 0.172). However, pain was correlated with the reported ocular discomfort, i.e., a pooled index of foreign body sensation, photophobia, burning sensation, and tearing (P < 0.001), and also with the pooled index of ocular inflammatory signs (conjunctival injection and eyelid edema) (P = 0.027). CONCLUSION: Crude density of corneal nerves may not be a good predictor of post-PRK pain while wearing bandage contact lenses. The predominant pain mechanism appears to be of an inflammatory nature (not nociceptive or neuropathic).