From Dizziness and Hearing Loss to Coma: A Case of Basilar Artery Occlusion.

Basilar artery (BA) occlusion is a rare and devastating cause of ischemic stroke. Presenting symptoms are frequently non-specific and include dizziness, vertigo, nausea, vomiting, headache, and, rarely, hypoacusis. Clinical history and appropriate neurological evaluation are essential for diagnosis. We present the case of a 65-year-old female with dizziness, vomiting, dysarthria, and hearing loss, progressing to right-side hemiparesis and decreased level of consciousness culminating in a coma in just a few hours. She had an atherothrombotic BA occlusion and was submitted to mechanical thrombectomy with full artery recanalization, resulting in rapid neurological improvement in the first days after treatment and almost full recovery during the following months. Early suspicion of posterior circulation stroke from non-specific symptoms is paramount for correct diagnosis and timely treatment, which has an important impact on disability and mortality. Early and complete BA recanalization can result in a positive outcome in a disease that would otherwise be extremely severe. All physicians should be aware of a possible posterior circulation stroke in patients presenting with dizziness, vertigo, vomiting, or sudden hypoacusis and should meticulously search for specific signs or symptoms of neurological dysfunction such as nystagmus, gaze palsies, dysarthria, hemiparesis, or a decreased level of consciousness.

Anti-N-Methyl-D-Aspartate Receptor Encephalitis, A Diagnosis Not To Miss.

Anti-N-methyl-D-aspartate receptor (Anti-NMDAR) encephalitis is a rare autoimmune disease, characterized by the presence of neuropsychiatric symptoms. It is sometimes mistaken for a psychiatric disorder and other times not considered in the differential diagnosis of an encephalitic process. Correct identification of this disease and prompt treatment are key for optimal recovery, which might take weeks to months. Many patients manifest severe symptoms, with depressed level of consciousness, breathing dysfunction and dysautonomia requiring admission to the Intensive Care Unit (ICU). We report the case a young male patient with anti-NMDA encephalitis who presented typical neuropsychiatric symptoms. Despite being diagnosed and treated in a timely manner, he did not respond well to first-line immunotherapy and was admitted to the ICU with neurological, respiratory, and cardiovascular dysfunction. This resulted in prolonged hospital admission and many infectious complications. Despite the severity of the disease, the patient managed to recover in the months following discharge from hospital. LEARNING POINTS: Anti-NMDAR encephalitis is a clinical entity described relatively recently, typically manifesting as a neuropsychiatric disorder and which should be in the differential diagnosis of any case of encephalitis, especially in young patients.Important prognostic factors for anti-NMDA encephalitis are lack of clinical improvement within the first four weeks of treatment and need for admission to the ICU.Anti-NMDAR encephalitis is a severe disease with good response to immunotherapy, hence the importance of a correct diagnosis. Nonetheless, recovery from severe disease may take months to years.

Relapsing Kikuchi-Fujimoto Disease With Hemophagocytic Lymphohistiocytosis.

Kikuchi-Fujimoto disease is a rare, benign, and self-limited disease of uncertain etiology, affecting mostly young female patients. It usually manifests as posterior cervical lymphadenopathy and fever. Its diagnosis is based on typical histopathological changes after the exclusion of other diseases such as lupus, lymphoma, or infectious lymphadenitis. The authors present a 47-year-old female patient with recurring episodes of high fever, urticarial rash, myalgia, arthralgia, fatigue, sore throat, and generalized lymphadenopathy. Blood tests showed increased inflammatory parameters and positive antinuclear antibodies. In the two times the patient was admitted to the hospital there were no infectious agents isolated. The patient didn't fulfill the criteria for diagnosis of lupus or any other autoimmune disease and there was also no evidence of lymphoma or other neoplastic diseases. A positron emission tomography/computed tomography (PET/CT) was performed at the first and second hospitalizations, showing generalized lymphadenopathy. At the first hospitalization, a mediastinal lymph node biopsy was obtained, excluding lymphoproliferative or granulomatous disease. During the course of the second hospitalization, a cervical lymph node was excised for biopsy, the histopathological changes of which suggested the diagnosis of Kikuchi-Fujimoto disease. The clinical course was complicated by hemophagocytic lymphohistiocytosis, with a significant increase in inflammatory markers and liver dysfunction. The patient was treated with prednisolone 1 mg/kg/day, with complete resolution of clinical and biochemical changes.

An Acute Blue Finger: A Case of Achenbach's Syndrome.

Achenbach's syndrome, also known as paroxysmal finger haematoma, is a rare condition that results in spontaneous bruising and pain in one or more fingers. Despite its benign and self-limiting course, the remarkable clinical presentation can suggest serious vascular and haematological disease leading to unnecessary referrals and invasive investigations. The authors present the case of a 60-year-old woman with an acute painful and bruised finger. All other physical findings and investigations were normal, except for autoimmune thyroiditis. Based on the clinical presentation and course, the diagnosis of Achenbach's syndrome was made and the symptoms resolved without treatment. LEARNING POINTS: Achenbach's syndrome is a rare and benign condition characterized by recurrent episodes of sudden pain, bruising and swelling of one or more fingers.It is a self-limiting condition and the diagnosis is essentially based on history and clinical examination.It is important to recognize this rare syndrome in order to address patient concerns and avoid unnecessary referrals or invasive investigations.

Mycoplasma pneumoniae-associated Mucositis: A Recently Described Entity.

Mycoplasma pneumoniae (MP) is a common cause of respiratory infections and can be associated with extrapulmonary complications. MP mucositis has recently been described as a distinct endemic clinical entity called Mycoplasma pneumoniae-induced rash and mucositis (MIRM). The authors present the case of a 46-year-old man with atypical pneumonia associated with exuberant mucositis, conjunctival hyperaemia and positive serological assays for MP IgM. The patient was treated with azithromycin and systemic corticosteroid therapy. Supportive care including pain management, intravenous hydration and mucosal care was also given. There was complete resolution of the pneumonia and mucositis. The presence of atypical pneumonia with mucosal involvement without cutaneous lesions and a favourable clinical evolution led to the diagnosis of MIRM. LEARNING POINTS: Mycoplasma pneumoniae infection can be associated with mucocutaneous lesions. A new entity called Mycoplasma pneumoniae-induced rash and mucositis (MIRM) has been recently described. The mucocutaneous involvement associated with MIRM is predominantly mucositis with scarce or absent cutaneous expression.The clinical presentation, pathophysiology and disease outcomes of MIRM distinguish it from Stevens-Johnson syndrome/toxic epidermal necrolysis and erythema multiform.MIRM has an overall favourable prognosis as the majority of patients recover without sequalae and recurrence is rare.

IL10 low-frequency variants in Behçet's disease patients.

AIM: To explain the missing heritability after the genome-wide association studies era, sequencing studies allow the identification of low-frequency variants with a stronger effect on disease risk. Common variants in the interleukin 10 gene (IL10) have been consistently associated with Behçet's disease (BD) and the goal of this study is to investigate the role of low-frequency IL10 variants in BD susceptibility. METHODS: To identify IL10 low-frequency variants, a discovery group of 50 Portuguese BD patients were Sanger-sequenced in a 7.7 kb genomic region encompassing the complete IL10 gene, 0.9 kb upstream and 2 kb downstream, and two conserved regions in the putative promoter. To assess if the novel variants are BD- and/or Portuguese-specific, they were assayed in an additional group of BD patients (26 Portuguese and 964 Iranian) and controls (104 Portuguese and 823 Iranian). RESULTS: Rare IL10 coding variants were not detected in BD patients, but we identified 28 known single nucleotide polymorphisms with minor allele frequencies ranging from 0.010 to 0.390, and five novel non-coding variants in five heterozygous cases. ss836185595, located in the IL10 3' untranslated region, was also detected in one Iranian control individual and therefore is not specific to BD. The remaining novel IL10 variants (ss836185596 and ss836185602 in intron 3, ss836185598 and ss836185604 in the putative promoter region) were not found in the replication dataset. CONCLUSION: This study highlights the importance of screening the whole gene and regulatory regions when searching for novel variants associated with complex diseases, and the need to develop bioinformatics tools to predict the functional impact of non-coding variants and statistical tests which incorporate these predictions.

Gene expression profiling and association studies implicate the neuregulin signaling pathway in Behçet's disease susceptibility.

Behçet's disease (BD) is a complex disease with genetic and environmental risk factors implicated in its etiology; however, its pathophysiology is poorly understood. To decipher BD's genetic underpinnings, we combined gene expression profiling with pathway analysis and association studies. We compared the gene expression profiles in peripheral blood mononuclear cells (PBMCs) of 15 patients and 14 matched controls using Affymetrix microarrays and found that the neuregulin signaling pathway was over-represented among the differentially expressed genes. The Epiregulin (EREG), Amphiregulin (AREG), and Neuregulin-1 (NRG1) genes of this pathway stand out as they are also among the top differentially expressed genes. Twelve haplotype tagging SNPs at the EREG-AREG locus and 15 SNPs in NRG1 found associated in at least one published BD genome-wide association study were tested for association with BD in a dataset of 976 Iranian patients and 839 controls. We found a novel association with BD for the rs6845297 SNP located downstream of EREG, and replicated three associations at NRG1 (rs4489285, rs383632, and rs1462891). Multifactor dimensionality reduction analysis indicated the existence of epistatic interactions between EREG and NRG1 variants. EREG-AREG and NRG1, which are members of the epidermal growth factor (EGF) family, seem to modulate BD susceptibility through main effects and gene-gene interactions. These association findings support a role for the EGF/ErbB signaling pathway in BD pathogenesis that warrants further investigation and highlight the importance of combining genetic and genomic approaches to dissect the genetic architecture of complex diseases.

Association study of IL10 and IL23R-IL12RB2 in Iranian patients with Behçet's disease.

OBJECTIVE: Independent replication of the findings from genome-wide association studies (GWAS) remains the gold standard for results validation. Our aim was to test the association of Behçet's disease (BD) with the interleukin-10 gene (IL10) and the IL-23 receptor-IL-12 receptor ß2 (IL23R-IL12RB2) locus, each of which has been previously identified as a risk factor for BD in 2 different GWAS. METHODS: Six haplotype-tagging single-nucleotide polymorphisms (SNPs) in IL10 and 42 in IL23R-IL12RB2 were genotyped in 973 Iranian patients with BD and 637 non-BD controls. Population stratification was assessed using a panel of 86 ancestry-informative markers. RESULTS: Subtle evidence of population stratification was found in our data set. In IL10, rs1518111 was nominally associated with BD before and after adjustment for population stratification (odds ratio [OR] for T allele 1.20, 95% confidence interval [95% CI] 1.02-1.40, unadjusted P [P(unadj) ] = 2.53 × 10(-2) ; adjusted P [P(adj) ] = 1.43 × 10(-2) ), and rs1554286 demonstrated a trend toward association (P(unadj) = 6.14 × 10(-2) ; P(adj) = 3.21 × 10(-2) ). Six SNPs in IL23R-IL12RB2 were found to be associated with BD after Bonferroni correction for multiple testing, the most significant of which were rs17375018 (OR for G allele 1.51, 95% CI 1.27-1.78, P(unadj) = 1.93 × 10(-6) ), rs7517847 (OR for T allele 1.48, 95% CI 1.26-1.74, P(unadj) = 1.23 × 10(-6) ), and rs924080 (OR for T allele 1.29, 95% CI 1.20-1.39, P = 1.78 × 10(-5) ). SNPs rs10489629, rs1343151, and rs1495965 were also significantly associated with BD in all tests performed. Results of meta-analyses of our data combined with data from other populations further confirmed the role of rs1518111, rs17375018, rs7517847, and rs924080 in the risk of BD, but no epistatic interactions between IL10 and IL23R-IL12RB2 were detected. Results of imputation analysis highlighted the importance of IL23R regulatory regions in the susceptibility to BD. CONCLUSION: These findings independently confirm, extend, and refine the association of BD with IL10 and IL23R-IL12RB2. These associations warrant further validation and investigation in patients with BD, as they may have implications for the development of novel therapies (e.g., immunosuppressive therapy targeted at IL-23p19).

[Rheumatic manifestations and neoplasms]. / Manifestações reumáticas e neoplasias.

Links between rheumatic manifestations and neoplasms are today an evidence. Certain syndromes have epidemiologic studies confirming strong association with malignancy, such as dermatomyositis and polymyositis, hyperthrophic osteoarthropathy and Lambert - Eaton myasthenic syndrome. These disorders may mimic idiopathic conditions, difficulting diagnosis. Besides that, longstanding rheumatic syndromes may, in their course, behave like premalignant conditions, as a result of their pathophysiology or drugs used in their treatment. The mechanisms whereby the neoplasm leads to rheumatic symptoms are: direct invasion of the musculoskeletal system, synovial reaction of justa-articular bony or capsular carcinomatous, secondary gout and paraneoplastic manifestations. Neoplasms constitute an important admission cause in Internal Medicine wards and rheumatic manifestations are common causes of Internal Medicine and Rheumatology appointments. The objective of the present work is to review the literature concerning rheumatic syndromes more frequently associated with malignancy, characterizing features that may suggest the presence of a hidden neoplasm as well as the potential diagnostic and prognostic value of their presence in malignant diseases.