Thunderclap headache attributed to reversible cerebral vasoconstriction: view and review

Thunderclap headache attributed to reversible cerebral vasoconstriction (THARCV) is a syndrome observed in a number of reported cases. In this article we reviewed this new headache entity (idiopathic form) using the clinical-radiological findings of 25 reported patients. In this series of patients 72% were women, the mean age at the onset of first headache episode was 39.4 +/- 2.3 years. In addition to the sine quanon condition of being abrupt and severe (thunderclap) at the onset, the headache was usually described as being explosive, excruciating, or crushing. The feature of pulsatility, accompanied or not by nausea was described by 80% of the patients. Forty percent of the cases manifested vomiting and 24% photophobia. Usually the headache was generalized, and in three cases it was unilateral at least at the onset. In 21 of 25 patients (84%) there was at least one recurrence or a sudden increase in the intensity of the headache. A past history of migraine was present in 52% of the patients. Precipitating factors were identified in 56% of the patients. Sexual intercourse was described by six patients. Of the 25 patients with THARCV syndrome studied, 12 (48%) developed focal neurological signs, transitory ischemic attack (n = 1), or ischemic stroke (n = 11, 44%), and two (8%) of them manifested seizures. The THARCV syndrome is a neurological disturbance perhaps more frequent than expected, preferentially affecting middle aged female migraineurs, and having an unpredictable prognosis, either showing a benign course or leading to stroke.

ASSOCIATION BETWEEN SADDLE NOSE DEFORMITY AND RETRO-ORBITAL MASS IN WEGENER`S GRANULOMATOSIS

Objectives: The relationship between saddle nose deformity (SND) in Wegener`s granulomatosis (WG) and other clinical features, including retro-orbital mass formation (ROM), has been poor described. Therefore, this relationship was analyzed retrospectively from 2000 to 2010. Patients and Methods: Eighteen consecutive WG patients with SND diagnosed by computed tomography were matched to 36 WG patients without SND (control group) for gender, age at WG diagnosis and disease duration. Results: No difference was found between the two groups in relation to WG type (limited and systemic forms), ethnicity, laboratory features, constitutional symptoms or clinical manifestations, including upper respiratory tract, and treatment, except for ROM (33.3 vs. 2.8% in SND(+) and SND(-) groups, respectively; p=0.004) and subglottic stenosis (22.2 vs. 2.8%; p=0.038). However, on multivariate analysis, only ROM (OR 17.15; 95% CI 1.11-265.52) was statistically associated to SND. In addition, in more than half of the cases, SND manifested prior to ROM. Conclusions: Results of this prospective analysis showed that SND was strongly associated to ROM in WG. Since early diagnosis and aggressive treatment of orbital involvement could lead to better prognosis, the presence of SND warrants additional vigilance.

EULAR/PRINTO/PRES criteria for Henoch-Schonlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Part II: Final classification criteria

Objectives To validate the previously proposed classification criteria for Henoch-Schonlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu arteritis (c-TA). Methods Step 1: retrospective/prospective webdata collection for children with HSP, c-PAN, c-WG and c-TA with age at diagnosis <= 18 years. Step 2: blinded classification by consensus panel of a representative sample of 280 cases. Step 3: statistical (sensitivity, specificity, area under the curve and.-agreement) and nominal group technique consensus evaluations. Results 827 patients with HSP, 150 with c-PAN, 60 with c-WG, 87 with c-TA and 52 with c-other were compared with each other. A patient was classified as HSP in the presence of purpura or petechiae (mandatory) with lower limb predominance plus one of four criteria: (1) abdominal pain; (2) histopathology (IgA); (3) arthritis or arthralgia; (4) renal involvement. Classification of c-PAN required a systemic inflammatory disease with evidence of necrotising vasculitis OR angiographic abnormalities of medium-/small-sized arteries (mandatory criterion) plus one of five criteria: (1) skin involvement; (2) myalgia/muscle tenderness; (3) hypertension; (4) peripheral neuropathy; (5) renal involvement. Classification of c-WG required three of six criteria: (1) histopathological evidence of granulomatous inflammation; (2) upper airway involvement; (3) laryngo-tracheo-bronchial involvement; (4) pulmonary involvement (x-ray/CT); (5) antineutrophilic cytoplasmic antibody positivity; (6) renal involvement. Classification of c-TA required typical angiographic abnormalities of the aorta or its main branches and pulmonary arteries (mandatory criterion) plus one of five criteria: (1) pulse deficit or claudication; (2) blood pressure discrepancy in any limb; (3) bruits; (4) hypertension; (5) elevated acute phase reactant. Conclusion European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society propose validated classification criteria for HSP, c-PAN, c-WG and c-TA with high sensitivity/specificity.

Wegener`s granulomatosis: experience from a Brazilian tertiary center

Most epidemiological studies with Wegener`s granulomatosis (WG) patients are based on populations from the Northern hemisphere, whereas very few studies have been conducted in Southern hemisphere populations, particularly from South America. The authors performed a large retrospective, demographic study including clinical and laboratory profiles of 134 consecutive WG patients seen at one Brazilian center from 1999 to 2009. Mean age at initial WG diagnosis was 43.4 +/- 15.5 years, and mean disease duration was 8.6 +/- 6.6 years. Sixty-four (47.8%) patients were male and a total of 113 (84.3%) subjects were white. Ear/nose/throat involvement occurred in 85.8%. The classic lung and renal involvement were observed in 77.6% and 75.4%, respectively, followed by ocular (35.8%), musculoskeletal (33.4%), cutaneous (29.1%), neurological (20.1%), cardiac (11.2%), and genitourinary involvement in 2.2% of cases. Cytoplasmic pattern-antineutrophil cytoplasmic antibody was detected in 83 (61.9%) cases. Ten (7.5%) individuals presented limited forms of WG. Classic therapy with corticosteroids and cyclophosphamide was used in 97 cases (72.4%). There were no cases of tuberculosis or Pneumocystis jiroveci pneumonia, but cutaneous herpes zoster occurred in eight (6.0%) individuals. There were 29 deaths (21.6%). Eighteen patients died of septic shock (mainly bacterial pneumonia), whereas four died of alveolar hemorrhage, four of myocardial infarction, and three of other causes. In summary, our data from a very large retrospective and descriptive study mirrored the main clinical features of WG described in other countries, demonstrating that they may serve as a reference for South American populations.

Hypertonic saline reduces metalloproteinase expression in liver during pancreatitis

P>We recently demonstrated that hypertonic saline reduces inflammation and mortality in acute pancreatitis. The present study investigated the effects of hypertonic saline in metalloproteinase (MMP) regulation and pancreatitis-associated hepatic injury. Wistar rats were divided into four groups: (i) control, not subjected to insult or treatment; (ii) no treatment (NT), induction of pancreatitis (retrograde infusion of 2.5% sodium taurocholate (1.0 mL/kg)), but no further treatment; (iii) normal saline (NS), induction of pancreatitis and treatment with normal saline (0.9% NaCl, 34 mL/kg, i.v. bolus, 1 h after the induction of pancreatitis); and (iv) hypertonic saline (HS), induction of pancreatitis and treatment with hypertonic saline (7.5% NaCl, 4 mL/kg administered over a period of 5 min, 1 h after the induction of pancreatitis). In all four groups, 4, 12 and 24 h after the induction of pancreatitis, liver tissue samples were assayed to determine levels of MMP-2, MMP-9, 47 kDa heat shock protein (HSP47) and collagen (Type I and III). Compared with the control group, MMP-9 expression and activity was increased twofold in the NS and NT groups 4 and 12 h after the induction of pancreatitis, but remained at basal levels in the HS group. In contrast, MMP-2 expression was increased twofold 12 h after the induction of pancreatitis only in the NS group, whereas the expression of HSP47 was increased 4 h after the induction of pancreatitis in the NS and NT groups. Greater extracellular matrix remodelling occurred in the NS and NT groups compared with the HS group, probably as a result of the hepatic wound-healing response to repeated injury. However, the collagen content in hepatic tissue remained at basal levels in the HS group. In conclusion, the results of the present study indicate that hypertonic saline is hepatoprotective and reduces hepatic remodelling, maintaining the integrity of the hepatic extracellular matrix during pancreatitis. Hypertonic saline-mediated regulation of MMP expression may have clinical relevance in pancreatitis-associated liver injury.

Concomitant Lucio Phenomenon and Erythema Nodosum in a Leprosy Patient: Clues for Their Distinct Pathogeneses

Lepromatous leprosy patients may develop necrotic lesions, usually in the context of Lucio phenomenon (LP) or severe erythema nodosum (EN). The clinical and histopathological characteristics of the necrotic manifestations of both entities may eventually be confounded. We describe a patient with lepromatous leprosy who developed, since the 4th month of her first pregnancy, recurrent necrotic lesions in lower limbs, which, at the postpartum, worsened and led to partial destruction of ears and nose. In addition, she referred painful nodes oil upper limbs since I year before pregnancy and intermittent swelling and tenderness of the ankles, which together with a right tibial and ulnar neuritis led to the diagnosis of, erythema nodosum leprosum (ENL). The histopathology of a biopsy of the upper limb (ENL) revealed a dermal-hypodermal inflammation with vasculitis and vascular lumen narrowing, whereas biopsy of the lower limb (LP) revealed small vessels with fibrin thrombi on the superficial layer of the dermis without inflammatory infiltrate and no evidence of vasculitis. Thus, besides having several different clinical features, LP and ENL result from different pathogenetic mechanisms. The histopathological and clinical features distinguishing both entities are proposed. This distinction is important because decrease in bacillary load through multidrug therapy is the main target in LP, whereas in ENL, concomitant reduction of the reaction by means of thalidomide or high-dose steroids is recommended.

Early neonatal morbidity and mortality in growth-discordant twins

Objective. To evaluate early neonatal morbidity and mortality in twin pregnancies with growth discordance. Design. Retrospective study. Setting. Tertiary teaching hospital, Sao Paulo, Brazil. Population. A total of 151 twin pregnancies managed and delivered at the Multiple Pregnancy Unit at Sao Paulo University Hospital between 1998 and 2004. Methods. Comparison between twin pregnancies with weight discordance 20% and pregnancies concordant for fetal weight. Cases with fetal death, abnormalities, twin-to-twin transfusion and delivery before 26 weeks or in another hospital were excluded. Outcome measures. Early neonatal morbidity (Apgar at 5 minutes 7, respiratory or neurological complications, infection, necrotizing enterocolitis, length of hospital stay) and mortality. Results. Forty (26.5%) pregnancies presented discordance 20% and 111 (73.5%) were concordant. In the discordant group, 75% of pregnancies had at least one growth restricted fetus (10th centile). In concordant twin pregnancies, monochorionic cases (22.5%) presented with lower gestational age (34.3 vs. 36.2 weeks), lower birthweight (2,067 vs. 2,334 g) and a longer period of hospital stay (5.5 vs. 3.0) compared to dichorionic concordant twins. No differences between monochorionic and dichorionic subgroups were observed in discordant twins. Pregnancies in which at least one baby was born with a birthweight below the 10th centile showed that discordant pregnancies had a lower gestational age at delivery (35.2 vs. 36.8 weeks) and a longer period of hospital stay (9 vs. 4 weeks) compared to concordant cases. Neonatal mortality was similar in discordant (3.7%) and concordant (4.5%) twins. Conclusion. Early perinatal morbidity is increased in twin pregnancies with birthweight discordance 20% only when associated with fetal growth restriction and low birthweight.

Lung Pathology in Fatal Novel Human Influenza A (H1N1) Infection

Rationale: There are no reports of the systemic human pathology of the novel swine H1N1 influenza (S-OIV) infection. Objectives: The autopsy findings of 21 Brazilian patients with confirmed S-OIV infection are presented. These patients died in the winter of the southern hemisphere 2009 pandemic, with acute respiratory failure. Methods: Lung tissue was submitted to virologic and bacteriologic analysis with real-time reverse transcriptase polymerase chain reaction and electron microscopy. Expression of toll-like receptor (TLR)-3, IFN-gamma, tumor necrosis factor-alpha, CD8(+) T cells and granzyme B(+) cells in the lungs was investigated by immunohistochemistry. Measurements and Main Results: Patients were aged from 1 to 68 years (72% between 30 and 59 yr) and 12 were male. Sixteen patients had preexisting medical conditions. Diff use alveolar damage was present in 20 individuals. in six patients, diffuse alveolar damage was associated with necrotizing bronchiolitis and in five with extensive hemorrhage. There was also a cytopathic effect in the bronchial and alveolar epithelial cells, as well as necrosis, epithelial hyperplasia, and squamous metaplasia of the large airways. There was marked expression of TLR-3 and IFN-gamma and a large number of CD8(+) T cell sand granzyme B(+) cells within the lung tissue. Changes in other organs were mainly secondary to multiple organ failure. Conclusions: Autopsies have shown that the main pathological changes associated with S-OIV infection are localized to the lungs, where three distinct histological patterns can be identified. We also show evidence of ongoing pulmonary aberrant immune response. Our results reinforce the usefulness of autopsy in increasing the understanding of the novel human influenza A (H1N1) infection.

PENILE AND SCROTUM SWELLING IN JUVENILE DERMATOMYOSITIS

Edema is a well-known feature of juvenile dermatomyositis (JDM). However, to our knowledge localized penile and scrotum swelling was not previously reported. During a 27-year period, 5,506 patients were followed up at the Pediatric Rheumatology Unit of our University Hospital and 157 patients (2.9%) had JDM. One of them (0.6%) had concomitant localized penile and scrotum swelling. He had severe disease activity since he was 7-year-old, manifested by diffuse cutaneous vasculitis, recurrent localized edema (limbs or face) and only one episode of generalized edema. At the age of 10, he presented edema of the genitalia associated with mild skin erythema. Penis, scrotum and testicular ultrasound as well as magnetic resonance imaging showed skin edema without testicular involvement. He was taking prednisone, methotrexate, cyclosporin, hydroxychloroquine and thalidomide. Improvement of skin rash, penile and scrotum swelling was noticed only with rituximab therapy. No adverse event was observed during anti-CD20 infusions and after six months of follow up. Penile and scrotum edema was a rare manifestation of JDM which improved with anti-CD20 monoclonal antibody treatment.

Frequency of thrombophilia determinant factors in patients with livedoid vasculopathy and treatment with anticoagulant drugs - a prospective study

Background Livedoid vasculopathy (LV) is a chronic idiopathic disease characterized by painful purpuric macules on lower extremities. Its exact aetiology remains uncertain, but thrombotic and microcirculatory phenomena have been implicated as possible pathogenic factors. Objectives To assess prospectively the frequency of thrombophilia and to verify the effectiveness of anticoagulant therapy among LV patients. Methods Thirty-four LV patients were tested for prothrombin time, activated partial thromboplastin time, antithrombin activity, protein C and S activity, anticardiolipin antibodies, lupus anticoagulant, prothrombin gene mutation, factor V Leiden mutation, methylenetetrahydrofolate reductase mutation, plasma homocysteine and fibrinogen. Thirteen of these patients were treated with anticoagulant drugs (either warfarin or heparin). Results Of 34 patients, 18 (52%) presented laboratory abnormalities of procoagulant conditions. Positive treatment response to anticoagulant therapy was observed in 11 patients. Improvement of pain was obtained in 1-3 weeks, an average of 1.8 week. Complete healing of the lesions was observed in about 2.3 months. Remission was sustained even after treatment interruption and lasted an average 7.8 months. No severe adverse effects were noticed. Conclusion The authors suggest all patients with diagnosis of LV to be investigated for thrombophilic status. Anticoagulant drugs were well tolerated and seemed to be effective in treating not only LV symptoms but also its ulcerations.

Pathogenic role of anti-endothelial cell antibodies in autoimmune rheumatic diseases

Anti-endothelial cells antibodies have been detected in numerous autoimmune and inflammatory diseases, including systemic lupus erythematous, rheumatoid arthritis, vasculitis and sarcoidosis. Anti-endothelial cells antibodies bind to endothelial cell antigens and induce endothelial damage. Their effects on the endothelial cell have been considered responsible, at least in part, by the vascular injury which occurs in these pathological conditions. Lupus (2009) 18, 1233-1238.

High frequency of lipoprotein risk levels for cardiovascular disease in Takayasu arteritis

The objective of this study is to characterize the lipoprotein risk levels in Takayasu arteritis (TA) patients and its possible association with disease activity and glucocorticoid use. Twenty-five female TA patients were consecutively included and compared with 30 age-, gender-, and body mass index-matched healthy controls. Demographic features and the lipid profile were determined and cardiovascular risk levels were evaluated according to NCEP/ATPIII. Total cholesterol (TC), LDL-c, HDL-c, and triglycerides were determined after a 12-h overnight fast. Exclusion criteria were conditions that interfere in the lipid profile. The disease duration was 6.6 +/- 7.4 years; 30% had clinical activity and 80% had laboratory activity. Regarding NCEP/ATPIII risk levels, TA patients presented higher frequency of lipid risk compared to controls: high TC (48% vs. 20%, p = 0.04), low HDL-c (20% vs. 0%, p = 0.015), and high triglycerides (36% vs. 10%, p = 0.026). No difference was observed related to LDL-c risk levels between both groups (40% vs. 20%, p = 0.14). Remarkably, 60% of the patients had at least one lipid risk factor for cardiovascular disease. No difference in the lipids was observed between patients with and without clinical activity; however, those with laboratory activity showed lower levels of HDL-c (1.37 +/- 0.42 vs. 2.00 +/- 0.63 mmol/L, p = 0.012) than patients without this activity. A negative correlation was found between HDL-c and CRP levels (r = -0.42, p = 0.04). Lipids were similar in patients under glucocorticoid compared to those without this therapy. This is the first study to identify that TA, an inflammatory disease, has a proatherogenic lipid profile which is associated to laboratory disease activity.

Hemorrhagic vesicle-bullous lesions in Henoch-Schonlein purpura and review of literature

Introduction: The characteristic feature of Henoch-Schonlein purpura (HSP) is palpable purpura, however hemorrhagic vesicles and blisters have been rarely reported. Case reports: From January 1983 to December 2007, 5079 patients were followed in our Pediatric Rheumatology Unit, 232 (4.6%) of them with the diagnosis of HSP. Three female patients (1.3%) presented hemorrhagic vesicles and bullous lesions associated with palpable purpura. In one case the lesions were severe and widespread, and in another they preceded the typical purpuric lesions. In both cases, skin biopsy disclosed leukocytoclastic vasculitis with IgA and C3 deposits. Two patients healed with residual lesions: ulcers in one case and skin hyperpigmentation in two of them. Discussion: Hemorrhagic vesicle-bullous lesions are rare in HSP This manifestation may represent a more severe and prolonged disease course with scars or may precede typical skin lesions.

Chronic autoimmune urticaria as the first manifestation of juvenile systemic lupus erythematosus

Chronic urticaria (daily or almost daily symptoms lasting for more than six weeks) is characterized by wheals and erythema, with or without itching. A few case reports have shown chronic autoimmune urticaria at the beginning of systemic lupus erythematosus (SLE), particularly in adults. However, the prevalence of this manifestation in a lupus paediatric population was not studied. During 27 consecutive years, 5419 patients were followed up at our University Hospital and 271 (5%) had juvenile SLE (American College of Rheumatology criteria). Two of them (0.7%) had chronic and painless autoimmune urticaria as the first manifestation of juvenile SLE, and were reported herein. One case was a five-year old female with continuous widespread urticaria (duration 120 days), antinuclear antibodies (ANA) 1:640 (dense fine speckled pattern) and elevated complement levels. The juvenile SLE diagnosis was established after one year. The other case was a 13-year old female who had chronic widespread urticaria (lasting 45 days), ANA 1:160 (fine speckled pattern) and normal complement levels. The juvenile SLE diagnosis was established after three years. In conclusion, chronic autoimmune urticaria is very rare and may be the first lupus manifestation, particularly associated with the presence of autoantibodies. This study reinforces the importance of a rigorous follow-up in children and adolescents suffering from autoimmune urticaria due to the possibility of connective tissue disorders, such as paediatric lupus. Lupus (2011) 20, 763-766.

Role of platelet-activating factor in the pathogenesis of 5-fluorouracil-induced intestinal mucositis in mice

Gastrointestinal mucositis is a common side effect of cancer chemotherapy. Platelet-activating factor (PAF) is produced during gut inflammation. There is no evidence that PAF participates in antineoplastic-induced intestinal mucositis. This study evaluated the role of PAF in 5-fluorouracil (5-FU)-induced intestinal mucositis using a pharmacological approach and PAF receptor knockout mice (PAFR(-/-)). Wild-type mice or PAFR(-/-) mice were treated with 5-FU (450 mg/kg, i.p.). Other mice were treated with saline or BN52021 (20 mg/kg, s.c.), an antagonist of the PAF receptor, once daily followed by 5-FU administration. After the third day of treatment, animals were sacrificed and tissue samples from the duodenum were removed for morphologic evaluation. In addition, myeloperoxidase activity and the cytokine concentration were measured. 5-FU treatment decreased the duodenal villus height/crypt depth ratio, increased MPO activity, and increased the concentration of TNF-alpha, IL-1 beta and KC in comparison with saline-treated animals. In PAFR(-/-) mice and PAFR antagonist-treated mice, 5-FU-dependent intestinal damage was reduced and a decrease in duodenal villus height/crypt depth ratio was attenuated. However, the 5-FU-dependent increase in duodenum MPO activity was not affected. Without PAFR activation, 5-FU treatment did not increase the TNF-alpha, IL-1 beta and KC concentration. In conclusion, our study establishes the role of PAFR activation in 5-FU-induced intestinal mucositis. This study implicates treatment with PAFR antagonists as novel therapeutic strategy for this condition.