B. Sopeña

Candida albicans Endophthalmitis in Brown Heroin Addicts: Response to Early Vitrectomy Preceded and Followed by Antifungal Therapy

The management of Candida albicans endophthalmitis in intravenous drug abusers (IVDAs) has yet to be established. Early vitrectomy was previously reported as a promising treatment for C. albicans endophthalmitis. In our series, C. albicans endophthalmitis was diagnosed for 15 IVDAs. Funduscopic examinations confirmed severe vitritis in 12 patients and chorioretinitis in three. Blood and vitreal cultures were positive for C. albicans for seven and eight patients, respectively. Patients with vitritis received antifungal therapy before and after vitrectomy. Amphotericin B or fluconazole therapy was given according to the physicians preference. Vitrectomy was defined as early if it was performed within 1 week after the diagnosis of vitritis. All seven patients who underwent early vitrectomy had a favorable response without complications. Two of three patients who underwent late vitrectomy developed blindness or scotoma. Blindness was also described in two patients with vitritis who did not undergo vitrectomy. Early vitrectomy preceded and followed by antifungal therapy seems to be appropriate management of vitritis in IVDAs.

Systemic involvement in primary Sjögren’s syndrome evaluated by the EULAR-SS disease activity index: analysis of 921 Spanish patients (GEAS-SS Registry)

OBJECTIVE To evaluate systemic involvement in primary SS in a large cohort of Spanish patients using the EULAR-SS disease activity index (ESSDAI) definitions. METHODS Systemic involvement was characterized using ESSDAI definitions for the 10 clinical domains (constitutional, lymphadenopathy, glandular, articular, cutaneous, pulmonary, renal, peripheral nervous system, central nervous system and muscular). ESSDAI scores at diagnosis, during follow-up and cumulated at the last visit were calculated. RESULTS The cohort consisted of 921 patients. After a mean follow-up of 75 months, 77 (8%) patients still had an ESSDAI score of zero at the last visit. Organ by organ, the percentage of patients who developed activity during the follow-up (ESSDAI score ≥ 1 at any time) ranged between 1.4% and 56%, with articular, pulmonary and peripheral neurological involvement being the most common. Logistic multivariate regression analysis showed the following features at diagnosis and had the closest association with systemic activity (statistically significant independent variables in at least two domains): cryoglobulinaemia in five domains; anaemia, lymphopenia and low C3 levels in three domains each and age <35 years in two domains. Sicca features, ANA and RF at diagnosis were not associated with a higher cumulated activity score in any clinical domain. CONCLUSION Primary SS is undeniably a systemic disease, with the joints, lungs, skin and peripheral nerves being the most frequently involved organs. Cytopenias, hypocomplementaemia and cryoglobulinaemia at diagnosis strongly correlated with higher cumulated ESSDAI scores in the clinical domains. Clinically the ESSDAI provides a reliable picture of systemic involvement in primary SS.

Isoniazid Hepatotoxicity among Drug Users: The Role of Hepatitis C

The incidence of and risk factors associated with hepatotoxicity in patients with chronic hepatitis have not been systematically studied. Therefore, we conducted a prospective study that included former drug users who were treated with isoniazid for latent tuberculosis infection. Of 415 patients, 20 (4.8%; 95% confidence interval [CI], 3-7.4) had hepatotoxicity diagnosed, and 6 (1.4%; 95% CI, 0.5-3.2) developed clinical hepatitis, none of whom had serious symptoms. The only 2 factors independently associated with isoniazid hepatotoxicity were excessive alcohol consumption (odds ratio [OR]; 4.2, 95% CI, 1.6-10.8; P=.002) and a high baseline alanine transaminase level (OR, 4.3; 95% CI, 1.6-11.4; P=.002). The presence of hepatitis C virus antibodies was associated with hepatotoxicity only on univariate analysis. Treatment with isoniazid in drug users appears to be safe and well tolerated, although frequent asymptomatic elevations in transaminase levels were observed.

Identification of the PTPN22 functional variant R620W as susceptibility genetic factor for giant cell arteritis

Objective To analyse the role of the PTPN22 and CSK genes, previously associated with autoimmunity, in the predisposition and clinical phenotypes of giant cell arteritis (GCA). Methods Our study population was composed of 911 patients diagnosed with biopsy-proven GCA and 8136 unaffected controls from a Spanish discovery cohort and three additional independent replication cohorts from Germany, Norway and the UK. Two functional PTPN22 polymorphisms (rs2476601/R620W and rs33996649/R263Q) and two variants of the CSK gene (rs1378942 and rs34933034) were genotyped using predesigned TaqMan assays. Results The analysis of the discovery cohort provided evidence of association of PTPN22 rs2476601/R620W with GCA (PFDR=1.06E-04, OR=1.62, CI 95% 1.29 to 2.04). The association did not appear to follow a specific GCA subphenotype. No statistically significant differences between allele frequencies for the other PTPN22 and CSK genetic variants were evident either in the case/control or in stratified case analysis. To confirm the detected PTPN22 association, three replication cohorts were genotyped, and a consistent association between the PTPN22 rs2476601/R620W variant and GCA was evident in the overall meta-analysis (PMH=2.00E-06, OR=1.51, CI 95% 1.28 to 1.79). Conclusions Our results suggest that the PTPN22 polymorphism rs2476601/R620W plays an important role in the genetic risk to GCA.

Autoimmune Manifestations of Kikuchi Disease

OBJECTIVES Kikuchis disease (KD) has been associated with the presence of autoantibodies, systemic lupus erythematosus (SLE), and other autoimmune diseases. The aim of this study was to assess the frequency of autoimmune manifestations in a KD cohort with a long follow-up. METHODS Twenty patients with histologically confirmed KD since January 1990 until December 2010 were studied; 12 of them were periodically followed up as outpatients. Another 7 patients were contacted by telephone to offer them a specific consultation and a complete autoimmunity study. RESULTS Thirteen of 20 patients were women (65%) with a mean age of 29 years (range, 15-79). The age at diagnosis was higher in men (44 vs 27 years, P < 0.05). Lymphopenia was present in 75% of the patients (15/20) and was the more frequent hematological abnormality. The mean follow-up of the 17 patients included in the autoimmunity study was 119 months (range, 15-252). Autoimmune diseases were detected in 9 women (53%): SLE was diagnosed in 4 patients (2 SLE before, 1 simultaneous, and 1 after KD), 2 patients developed primary Sjögrens syndrome after KD, 1 thyroiditis before KD, 1 SLE-like, and 1 antiphospholipid antibodies after KD. Leukocytoclastic vasculitis was found in 2 patients; 1 of them eventually developed SLE. Female sex, painful adenopathies, and cytopenias were significantly associated with autoimmune diseases. CONCLUSIONS Among patients with KD, only women developed autoimmune manifestations. Therefore, long-term follow-up and active surveillance of autoimmune diseases in patients with KD, especially women, are recommended.

Cerebral tuberculoma--a comparative study in patients with and without HIV infection.

The microbiological, clinical and radiological findings of cerebral tuberculomas in four patients with and in five patients without HIV infection were compared. The study was carried out during the last 14 years. The CT scans were analyzed in a blinded fashion. Cerebral tuberculoma in HIV-negative patients was clinically characterized by seizures, while in HIV-positive patients this finding was absent. All four HIV-infected patients had headache and fever and their CSF showed lymphocytic meningitis. Two HIV-negative and three HIV-positive patients had concurrent extracerebral tuberculosis. In HIV-infected patients, the cerebral tuberculoma was a secondary finding of disseminated tuberculosis. In our small patient samples, the cerebral tuberculoma presented as spontaneous hypodense cerebral lesions in all the HIV-positive patients but as a hyperdense cerebral lesion in the HIV-negative patients. Two patients of each group had ring enhancement lesions. Cerebral tuberculoma was diagnosed in about 4 weeks for HIV-positive patients, but took some 16 weeks for HIV-negative patients, the latter being first suspected of having a cerebral tumor or bacterial abscess. Diagnostic craniotomy was thus necessary for the HIV-negative patients. One patient of each group died as a consequence of cerebral tuberculoma, all the remaining patients improved with treatment. Die mikrobiologischen, klinischen und röntgenologischen Befunde eines zerebralen Tuberkuloms wurden bei vier Patienten mit und fünf Patienten ohne HIV-Infektion verglichen. Die Studie wurde während der vergangenen 14 Jahre durchgeführt. Die Computertomogramme (CT) wurden blind ausgewertet. Die klinische Symptomatik des zerebralen Tuberkuloms bei HIV-negativen Patienten ist durch Krampfanfälle charakterisiert, die bei HIV-positiven Patienten nicht beobachtet wurden. Alle vier HIV-infizierten Patienten hatten Kopfschmerzen und Fieber. Im Liquor wurde der Befund einer lymphozytären Meningitis erhoben. Zwei HIV-negative und drei HIV-positive Patienten hatten zugleich eine extrazerebrale Tuberkulose. Bei HIV-infizierten Patienten stellte das zerebrale Tuberkulom eine sekundäre Manifestation einer disseminierten Tuberkulose dar. In unserer kleinen Patientengruppe bot das zerebrale Tuberkulom im Spotan-CT bei HIV-positiven Patienten das Bild einer hypodensen Läsion, bei den HIV-negativen Patienten hingegen einer hyperdensen Läsion. Bei zwei Patienten jeder Gruppe fand sich eine Ringverstärkung. Das zerebrale Tuberkulom wurde bei den HIV-positiven Patienten etwa nach vier Wochen, bei einigen der HIV-negativen Patienten aber erst nach 16 Wochen diagnostiziert. Bei den letztgenannten Patienten bestand Verdacht auf einen Hirntumor oder einen bakteriellen Abszeß. Die diagnostische Kraniotomie war daher bei den HIV-negativen Patienten erforderlich. In je einem Fall führte das zerebrale Tuberkulom zum Tode, bei allen anderen Patienten trat nach Behandlung Besserung ein.

Influence of the IL17A locus in giant cell arteritis susceptibility

Objective Different lines of evidence have highlighted the role of IL-17A in the inflammatory process occurring in giant cell arteritis (GCA). The aim of the present study was to assess whether the IL17A locus influences GCA susceptibility and its clinical subphenotypes. Methods We carried out a large meta-analysis including a total of 1266 biopsy-proven GCA patients and 3779 healthy controls from four European populations (Spain, Italy, Germany and Norway). Five IL17A polymorphisms (rs4711998, rs8193036, rs3819024, rs2275913 and rs7747909) were selected by tagging and genotyped using TaqMan assays. Allelic combination and dependency tests were also performed. Results In the pooled analysis, two of the five analysed polymorphisms showed evidence of association with GCA (rs2275913: PMH=1.85E−03, OR=1.17 (1.06–1.29); rs7747909: PMH=8.49E–03, OR=1.15 (1.04–1.27)). A clear trend of association was also found for the rs4711998 variant (PMH=0.059, OR=1.11 (1.00–1.23)). An independent effect of rs2275913 and rs4711998 was evident by conditional regression analysis. In addition, the haplotype harbouring the risk alleles better explained the observed association than the polymorphisms independently (likelihood p value <10−05). Conclusions Polymorphisms within the IL17A locus show a novel association with GCA. This finding supports the relevant role of the Th17 cells in this vasculitis pathophysiology.

High prevalence of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia

OBJECTIVE Hereditary hemorrhagic telangiectasia (HHT) is a vascular disorder causing mucocutaneous telangiectases and visceral arteriovenous malformations (AVMs). Pulmonary hypertension (PH) is considered an uncommon complication of HHT whose impact on the survival of these patients is currently unknown. METHODS From January 1995 to December 2008, 29 hospitalized patients with definite HHT were included and followed until January 2011. Data on demographics, clinical symptoms and survival were recorded. PH was classified according to echocardiographic probability. RESULTS A CT angiogram was performed in 24 of the 29 patients with HHT and AVMs were detected in 16 of them (67%): hepatic in 58%, pulmonary in 33% and spinal in 3%; 37% had both pulmonary and hepatic AVMs. Transthoracic Doppler echocardiography (TTE) was performed in 21 patients. PH was considered possible in 4 (14%) and probable in 9 (31%). The mean age at diagnosis was lower in patients with PH than in patients without PH (54±16.5 years vs 73±8.8 years, p=0.002). PH was more prevalent in patients with AVMs (56 vs. 23%, p=0.036). The mean follow-up of the entire cohort was 6±4.4 years (range: 2 months-17 years), during this time 18 patients died (62%; mean age 73±8.1 years). Patients with PH died at a younger age (68±8.4 vs. 79±2.7 years, p=0.015) than those without PH. CONCLUSIONS PH is a severe condition that significantly reduces survival on HHT patients. PH should be suspected in all HHT patients with dyspnea and hepatic AVMs.

Evidence of association of the NLRP1 gene with giant cell arteritis

Recent studies have focused attention on the involvement of NLRP1 to confer susceptibility for extended autoimmune/inflammatory disorders, being considered a common risk factor in autoimmunity.1–3 NLRP1 provides a scaffold for the assembly of the inflammasome that activates caspases 1 and 5, required for processing and activation of the proinflammatory cytokines interleukin 1β (IL-1β), IL-18 and IL-33 and promoting inflammation.4 In this study, we examined for the first time whether NLRP1 is associated with giant cell arteritis (GCA), a chronic systemic vasculitis affecting large and medium-sized arteries derived from the aorta, in particular the cranial branches of the carotid artery. GCA is the most common vasculitis in the elderly in Western countries with a female predominance.5 To investigate the possible genetic association of NLRP1 with this disease, we genotyped a single-nucleotide polymorphism (rs8182352), which has been reported to confer risk to the development of autoimmune processes in previous studies,1 ,2 in a total of 3583 individuals, comprising a discovery set from Spain (574 patients diagnosed with biopsy-proven GCA and 2366 healthy controls) and a replication set of subjects from Italy (111 biopsy-proven GCA patients and 532 controls) using a predesigned TaqMan allele discrimination assay. All individuals were of …

Steroids treatment of granulomatous hepatitis complicatingCoxiella burnetii acute infection

SummaryGranulomatous hepatitis associated withCoxiella burnetii acute infection has an adverse clinical course in some patients. Surprisingly, it does not respond to antibiotic but to steroids treatment. A hypersensitivity mechanism has been implicated. A case of granulomatous hepatitis complicatingC. burnetii acute infection is reported, which was refractory to antibiotics but, as in four other cases previously reported, showed a complete response to steroids. This case was found to support findings that moderate doses of steroids can be useful in patients with granulomatous hepatitis complicatingC. burnetii infection and showing no response to antibiotic treatment.