Intravenous Immunoglobulin for the Treatment of Quetiapin-Induced Bullous Pemphigoid in an HIV-Infected Patient

The authors present the case of a 48-year-old woman with HIV-­associated dementia treated with antiretroviral therapy and psychoactive drugs, to whom bullous pemphigoid(BP) was diagnosed. Given incomplete response to corticotherapy, and azathioprine-­induced bicytopenia,intravenous immunoglobulin(IVIG) was initiated. Despite transient disease control, recurrent flares suggested a persistent triggering factor. Specifically, quetiapin was implicated and discontinued with an immediate clinical response. Inadvertent re-­challenge with olanzapine(a related drug)led to a new eruption, confirming drug-­induced BP (DIBP). A total of six IVIG cycles were completed, without severe side effects to report, namely HIV disease progression. HIV-­related autoimmune bullous diseases are rare. Treatment of severe drug eruptions is primarily based on immunossupressive drugs, raising concerns regarding additional immunossupression. This case suggests IVIG as a valuable option for the treatment of BP in HIV patients. In addition, quetiapin should be added to the list of neuroleptics previously linked to DIBP.

Calciphylaxis: a Literature Review Based in Two Case Reports

Calciphylaxis is a rare and devastating obliterative vasculopathy, leading to ischemia and subcutaneous necrosis. In most cases it affects patients with renal disease and is associated with high morbidity and mortality. We present two case reports followed recently in our department, and a literature review on this topic. Case one refers to an 80 -year -old Caucasian woman with chronic kidney disease stage 5 and primary hyperparathyroidism with secondary brown tumour and calciphylaxis. Case two refers to a 59 -year -old Caucasian woman admitted with severe nephrotic syndrome associated with amyloidosis, that developed a catastrophic picture of calciphylaxis, ending in the patient’s death. There is a critical need to understand the pathogenesis of calciphylaxis. Its comprehension is the only way to improve the survival of these patients, and may help to elucidate the pathophysiology of vascular calcification in general. Educating physicians in the prevention and early detection of calciphylaxis is crucial. Only by increasing the knowledge about risk factors, pathophysiology, response to treatment and outcome, will we be able to improve prophylaxis and therapy of patients with calciphylaxis, decreasing the high mortality of this entity.

Hyper-IgD and Periodic Fever Syndrome: a New MVK Mutation (p.R277G) Associated with a Severe Phenotype

Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS; MIM#260920) is a rare recessively-inherited autoinflammatory condition caused bymutations in the MVK gene, which encodes for mevalonate kinase, an essential enzyme in the isoprenoid pathway. HIDS is clinically characterized by recurrent episodes of fever and inflammation. Herewe report on the case of a 2 year-old Portuguese boy with recurrent episodes of fever, malaise, massive cervical lymphadenopathy and hepatosplenomegaly since the age of 12 months. Rash, arthralgia, abdominal pain and diarrhea were also seen occasionally. During attacks a vigorous acute-phase response was detected, including elevated erythrocyte sedimentation rate, C-reactive protein, serum amyloid A and leukocytosis. Clinical and laboratory improvement was seen between attacks. Despite normal serum IgD level, HIDS was clinically suspected. Mutational MVK analysis revealed the homozygous genotype with the novel p.Arg277Gly (p.R277G) mutation, while the healthy non consanguineous parents were heterozygous. Short nonsteroidal anti-inflammatory drugs and corticosteroid courses were given during attacks with poor benefits, where as anakinra showed positive responses only at high doses. The p.R277Gmutation here described is a novel missense MVK mutation, and it has been detected in this casewith a severe HIDS phenotype. Further studies are needed to evaluate a co-relation genotype, enzyme activity and phenotype, and to define the best therapeutic strategies.

Short QT Syndrome Presenting As Syncope: How Short Is Too Short?

We report the case of a 52-year-old man who presented to our emergency department (ED) after three episodes of syncope in the seven hours before admission. During his stay in the ED he had recurrent ventricular tachycardia (VT) requiring external electrical cardioversion. A 12-lead electrocardiogram (ECG) showed a short QT (SQT) interval (270 ms, QTc 327 ms), with frequent R-on-T extrasystoles triggering sustained polymorphic VT. After exclusion of other precipitating causes, the patient was diagnosed as having SQT syndrome (SQTS) according to the Gollob criteria. To our knowledge, this is the first known documentation of an SQT-caused arrhythmic episode on a 12-lead ECG, as well as the first reported case of SQTS in Portugal. The patient received an implantable cardioverter-defibrillator and was discharged. At a follow-up assessment 14 months later he was symptom-free, interrogation of the device showed no arrhythmic events, and the ECG showed a QT interval of 320 ms (QTc 347 ms).

Impact of Syncope on Quality of Life: Validation of a Measure in Patients Undergoing Tilt Testing

INTRODUCTION AND OBJECTIVES: Recurrent syncope has a significant impact on quality of life. The development of measurement scales to assess this impact that are easy to use in clinical settings is crucial. The objective of the present study is a preliminary validation of the Impact of Syncope on Quality of Life questionnaire for the Portuguese population. METHODS: The instrument underwent a process of translation, validation, analysis of cultural appropriateness and cognitive debriefing. A population of 39 patients with a history of recurrent syncope (>1 year) who underwent tilt testing, aged 52.1 ± 16.4 years (21-83), 43.5% male, most in active employment (n=18) or retired (n=13), constituted a convenience sample. The resulting Portuguese version is similar to the original, with 12 items in a single aggregate score, and underwent statistical validation, with assessment of reliability, validity and stability over time. RESULTS: With regard to reliability, the internal consistency of the scale is 0.9. Assessment of convergent and discriminant validity showed statistically significant results (p<0.01). Regarding stability over time, a test-retest of this instrument at six months after tilt testing with 22 patients of the sample who had not undergone any clinical intervention found no statistically significant changes in quality of life. CONCLUSIONS: The results indicate that this instrument is of value for assessing quality of life in patients with recurrent syncope in Portugal.

Gastrinoma de Localização Pilórica numa Doente com Úlcera Péptica Recorrente

Apresenta-se o caso clínico de uma mulher de 56 anos, raça branca, com úlcera duodenal e esofagite com 3 anos de evolução apesar de terapêutica mantida com bloqueadores dos receptores H2. O valor da gastrina sérica basal estava ligeiramenteacima dos limites superiores do normal. O teste de estimulação de secretina foi sugestivo de gastrinoma. Com tomografia axial computorizada e arteriografia selectiva não se localizou o tumor. Na laparotomia exploradora encontrou-se um nódulo pilórico que se demonstrou corresponder ao gastrinoma. Dezoito meses após a cirurgia a doente encontrou-se assintomática e os exames de controle são negativos.

Perinatal Ischemic Stroke: a Five-Year Retrospective Study in a Level-III Maternity

Objective To study the incidence, clinical presentation, risk factors, imaging diagnosis, and clinical outcome of perinatal stroke. Methods Data was retrospectively collected from full-term newborns admitted to the neonatal unit of a level III maternity in Lisbon with cerebral stroke, from January 2007 to December 2011. Results There were 11 cases of stroke: nine were arterial ischemic stroke and two were cerebral venous sinus thrombosis. We estimated an incidence of arterial ischemic stroke of 1.6/5,000 births and of cerebral venous sinus thrombosis of 7.2/100,000 births. There were two cases of recurrent stroke. Eight patients presented with symptoms while the remaining three were asymptomatic and incidentally diagnosed. The most frequently registered symptoms (8/11) were seizures; in that, generalized clonic (3/8) and focal clonic (5/8). Strokes were more commonly left-sided (9/11), and the most affected artery was the left middle cerebral artery (8/11). Transfontanelle ultrasound was positive in most of the patients (10/11), and stroke was confirmed by cerebral magnetic resonance in all patients. Electroencephalographic recordings were carried out in five patients and were abnormal in three (focal abnormalities n=2, burst-suppression pattern n=1). Eight patients had previously identified risk factors for neonatal stroke which included obstetric and neonatal causes. Ten patients were followed up at outpatients setting; four patients developed motor deficits and one presented with epilepsy. Conclusions Although a modest and heterogeneous sample, this study emphasizes the need for a high level of suspicion when it comes to neonatal stroke, primarily in the presence of risk factors. The prevalence of neurological sequelae in our series supports the need of long-term follow-up and early intervention strategies.

Neuromyelitis Optica in Portugal (NEMIPORT) - A Multicentre Study

BACKGROUND: Neuromyelitis Optica (NMO) is an inflammatory demyelinating disease of the CNS. There have been few epidemiologic studies on NMO, none in Portugal. OBJECTIVE: To analyze the clinical, biological and MRI characteristics from a cohort of Portuguese patients who fulfilled the Wingerchuk 2006 NMO/NMOSD criteria. To identify and characterize those who had concomitant autoimmune disease or circulating autoantibodies. METHODS: We performed an observational, retrospective, multicenter study in 5 Hospital Centers in Portugal. RESULTS: Sixty-seven patients fulfilled the inclusion criteria. They were mainly Caucasian, 55 female. Median age at onset was 32.0 years and mean follow-up 7.4±6.0 years. Twenty-one patients were definite NMO and optic neuritis (ON) the most frequent initial presentation. Forty-six were classified as NMO spectrum disorders. The main subtypes were recurrent ON and single longitudinally extensive transverse myelitis. Twenty-four patients had positive AQP4-IgG. Twenty-three had other circulating autoantibodies. Fifteen out of 67 patients had concomitant autoimmune disease. There was a significant correlation between the presence of autoimmune disease and the positivity for AQP4-IgG. Five patients died, all definite NMO. CONCLUSION: This is the first study about this rare disease in Portugal. Demographic features were similar to other studies. The existence of concomitant autoimmune disease was significantly associated with seropositivity for AQP4-IgG.

Ophthalmoplegic Migraine and Infundibular Dilatation of a Cerebral Artery

Ophthalmoplegic migraine (OM) is a childhood disorder of uncertain etiology manifesting recurrent unilateral headache associated with a transitory oculomotor (usually IIIrd nerve) palsy. Recent publications emphasize the finding on MRI of contrast enhancement in the IIIrd nerve suggesting that OM may be a recurrent inflammatory neuropathy. We report the case of a 7-year-old boy with typical symptoms of this disorder. Angio MR and Angio CT revealed the presence of an infundibular dilatation of a perforating branch of the posterior cerebral artery adjacent to the symptomatic IIIrd nerve. We speculate that this and perhaps other cases of OM may have a different pathophysiology related to compression of the IIIrd nerve by an adjacent vascular structure that could activate the trigeminovascular system and produce migrainous pain.

Benefits of Selective Vitamin D Receptor Activators in Kidney Transplanted Patients

Severe chronic kidney disease may lead to disturbances, such as hyperphosphatemia, increased secretion of fibroblast growth factor -23 (FGF -23) and vitamin D deficiency. These may increase plasmatic levels of parathyroid hormone, and decrease plasmatic levels of calcium. Altogether, these may contribute to the development of secondary hyperparathyroidism, and to abnormalities in mineral metabolism. Kidney transplantation is the best option to improve longevity and quality of life in end -stage chronic kidney disease patients. Vitamin D deficiency has been associated with cardiovascular disease, which is the leading cause of death in chronic kidney disease. Therefore, diagnosing this deficiency may be pivotal for minimizing mortality in chronic kidney disease, because pharmacological treatments for this deficiency may be prescribed. Calcitriol is indicated for the treatment of vitamin D deficiency, both in chronic kidney disease and in kidney transplanted patients. However, calcitriol may increase the plasmatic levels of calcium and phosphorous, which can lead to vascular calcifications, that have been associated with cardiovascular mortality. Selective vitamin D receptor activators are indicated for the treatment of vitamin D deficiency in chronic kidney disease. These have the advantage of being associated with lower increases of plasmatic levels of calcium and phosphorous. These drugs also seem to have additional effects that may minimise patient morbidity and mortality, especially due to potentially reducing cardiovascular events. Unfortunately, there are few studies about the use of these drugs in kidney transplanted patients. Here we present a review about the physiology of vitamin D, the consequences of its deficiency in chronic kidney disease and in kidney transplanted patients, and about the diagnosis and treatment of this deficiency. Finally, we discuss the new line of research about the efficacy and safety of selective vitamin D receptor activators in kidney transplanted patients.

Acute Otitis Media a Reliable Warning Sign for Primary Immunodeficiencies?- A Critical Appraisal

Acute otitis media (AOM) is the most common infection in childhood, resulting from both anatomic and immunologic specificities of this age group. Recurrent AOM has been defined as one of the warning signs for primary immunodeficiencies (PID), In this study we evaluated the strength of recurrent AOM as clinical predictor of PID. Methods: Retrospective study (August 2010 - December 2013) which included all patients referred to PID appointment because of recurrent AOM (= 8 AOM episodes/year). Syndromic patients or those presenting with another warning sign for PID were excluded. Clinical, demographic and laboratory results were analized and statistical analysis was made using SPSS 20. Results: Seventy-five patients were included (median age 37,8 months; 62,7% male gender), corresponding to 15% of all first appointments. Other comorbidities were present in 20% of the patients and 17% had ORL surgery prior to PID referral. In most patients, the immunologic screening consisted on the evaluation of humoral function, but in selected cases other studies were performed (namely complement and lymphocyte immunophenotyping). A PID was identified in 12 children (16,0%) and the majority of these patients had other distinctive feature (personal or familiar antecedent of infection or auto-immunity, 66,7%, p<0,05). Nine children (12,0%) underwent prophylactic cotrimoxazole. The average length of follow-up was 11,2 months. Conclusion: Despite being a very frequent cause of immunologic screening, in this study recurrent AOM was not found to be a good predictor of underlying PID, unless the patients presents other significant personal or family history.

Identification of de Novo Germline Mutations in the HRPT2 Gene in Two Apparently Sporadic Cases with Challenging Parathyroid Tumor Diagnoses

The diagnosis of parathyroid carcinomas is often difficult. HRPT2 mutations have been identified in familial [hyperparathyroidism-jaw tumor (HPT-JT) syndrome] and sporadic parathyroid carcinomas, supporting that HRPT2 mutations may confer a malignant potential to parathyroid tumors. In this study, we report the clinical, histopathological, and genetic investigation of two unrelated cases, whom had apparently sporadic malignant parathyroid tumors, initially diagnosed as adenomas. In one case, the differential diagnosis was complicated by cervical seeding of parathyroid tumor cells. Genetic studies identified de novo HRPT2 germline mutations in cases 1 (c.518_521delTGTC [p.Ser174LysfsX27]) and 2 (c.226 C > T [p.Arg76X]), unveiling the hereditary HPT-JT syndrome in both patients. Furthermore, the identification of somatic mutations in the patients‟ parathyroid tumors provided evidence for complete inactivation of the HRPT2 gene, which was consistent with the tumor malignant features. The sensitivity of parafibromin immunostaining to detect HRPT2 mutations was limited. The present data suggests that patients with apparently sporadic parathyroid carcinomas, or parathyroid tumors with atypical histological features, should undergo molecular genetic testing, as it may detect germline HRPT2 mutations. Establishing the diagnosis of hereditary HPT-JT syndrome is relevant for clinical counseling and management of the carriers and their relatives.

Recursive neuro fuzzy techniques for online identification and control

Dissertação para obtenção do Grau de Mestre em Engenharia Electrotécnica e de Computadores

Pyoderma gangrenosum and ulcerative colitis in the tropics

Pyoderma gangrenosum is a rare inflammatory skin condition, characterized by progressive and recurrent skin ulceration. There may be rapidly enlarging, painful ulcers with undermined edges and a necrotic, hemorrhagic base. Disorders classically associated with pyoderma gangrenosum include rheumatoid arthritis, inflammatory bowel disease, paraproteinemia and myeloproliferative disorders. There have been some reports of the occurrence of pyoderma gangrenosum in Africa, and in Nigeria, but only one specifically reported pyoderma gangrenosum in association with ulcerative colitis. We report on a 45-year-old man who presented with pyoderma gangrenosum associated with ulcerative colitis; the second report in Nigeria. The skin lesions were managed with daily honey wound dressings. Oral dapsone and prednisolone were started. The frequency of the bloody diarrhea decreased, and was completely resolved by the second week after admission. The ulcers also showed accelerated healing. The goal of therapy is directed towards the associated systemic disorder, if present.

Restriction enzyme analysis of the human cytomegalovirus genome in specimens collected from immunodeficient patients in Belém, State of Pará, Brazil

INTRODUCTION: Human cytomegalovirus is an opportunistic betaherpesvirus that causes persistent and serious infections in immunodeficient patients. Recurrent infections occur due to the presence of the virus in a latent state in some cell types. It is possible to examine the virus using molecular methods to aid in the immunological diagnosis and to generate a molecular viral profile in immunodeficient patients. The objective of this study was to characterize cytomegalovirus genotypes and to generate the epidemiological and molecular viral profile in immunodeficient patients. METHODS: A total of 105 samples were collected from immunodeficient patients from the City of Belém, including newborns, hemodialysis patients, transplant recipients and HIV+ patients. An IgG and IgM antibody study was completed using ELISA, and enzymatic analysis by restriction fragment length polymorphism (RFLP) was performed to characterize viral genotypes. RESULTS: It was observed that 100% of the patients had IgG antibodies, 87% of which were IgG+/IgM-, consistent with a prior infection profile, 13% were IgG+/IgM+, suggestive of recent infection. The newborn group had the highest frequency (27%) of the IgG+/IgM+ profile. By RFLP analysis, only one genotype was observed, gB2, which corresponded to the standard AD169 strain. CONCLUSIONS: The presence of IgM antibodies in new borns indicates that HCMV continues to be an important cause of congenital infection. The low observed genotypic diversity could be attributed to the small sample size because newborns were excluded from the RFLP analysis. This study will be continued including samples from newborns to extend the knowledge of the general and molecular epidemiology of HCMV in immunodeficient patients.