Cinzia Buligan

BsmI, ApaI and TaqI polymorphisms in the Vitamin D Receptor gene (VDR) and association with lumbar spine pathologies: An Italian case-control study

Three adjacent single nucleotide polymorphisms of the vitamin D receptor gene (VDR) BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) are commonly studied in several pathologies. We aimed to evaluate the distribution of VDR BsmI, ApaI, and TaqI allele, genotype, and haplotype frequencies in an Italian cohort of 266 patients with lumbar spine disorders assessed by Magnetic Resonance Imaging and 252 asymptomatic controls. The exposure to putative risk factors was evaluated by a questionnaire. Polymorphisms were detected by PCR-RFLP and TaqMan® SNP Genotyping Assay. The results were statistically adjusted for the identified conventional risk factors. The three SNPs were in linkage disequilibrium. For all cases BbAaTT was a 3-fold risk factor OR = 3.38), whereas bbAATT (OR = 0.22), and bbaaTT (OR = 0.47) genotypes were found to be protective. Specifically, for patients affected by disc herniation only (n = 88) and all lumbar pathologies excluding stenosis and/or spondylolistesis (n = 215) B allele, Bb, Aa, and BbAaTT genotypes were risky, whereas b allele, bb, aa, and bbaaTT genotypes were protective. In patients affected by osteochondrosis with or without disc hernation (n = 50), T allele, Aa, and bbAaTT genotypes were risky, whereas t allele, AA, tt genotypes were protective. In patients affected by stenosis and/or spondylolistesis (n = 51) no significant associations were found. This is the first study showing an association of the three genetic VDR variants BsmI, ApaI, and TaqI and lumbar spine pathologies. Our study contributes to delineate genetic risk factors for specific subgroups of patients with lumbar spine pathologies highlighting the importance of haplotype analysis, and of detailed clinical evaluation of the patients for identification of genetic biomarkers.

Videocapillaroscopic findings in the microcirculation of the psoriatic plaque during etanercept therapy.

Vascular endothelial growth factor (VEGF) is a pivotal cytokine in the pathogenesis of psoriasis, and upregulation of VEGF by tumour necrosis factor (TNF)‐α and inflammatory factors causes marked alterations in the cutaneous microcirculation. Etanercept is a fully soluble TNF receptor fusion protein that primarily binds soluble TNF‐α, thus blocking its pro‐angiogenic function.

Clinical and Capillaroscopic Modifications of the Psoriatic Plaque during Therapy: Observations with Oral Acitretin

Psoriasis is considered to be an inflammatory autoimmune disease, where angiogenesis plays an undefined pathogenetic role. The well-known changes of the superficial microvasculature in the psoriatic plaque can be easily assessed in vivo by videocapillaroscopy. In the last years, several studies reported the clinical and capillaroscopic response of the psoriatic plaque during different topical and systemic treatments. In the present work we evaluated the effects of acitretin (0.8 mg/kg/day) on videocapillaroscopic alterations and the clinical response in 11 patients affected by plaque psoriasis at the baseline (T0) and after 4 (T1), 8 (T2), and 12 (T3) weeks. A clinical improvement during the treatment with a complete clinical healing of the plaque in 7 of the 11 patients was observed. The typical “basket-weave” capillaries of the psoriatic lesions showed a reduction of 65.4% in diameter at the end of the study; only 3 patients returned to a normal capillaroscopic pattern. As observed during previous our studies, we found a discrepancy between clinical and capillaroscopic results, with a far greater improvement in the first than in the second. This finding could be in agreement with a secondary role of blood vessels in the pathogenesis and persistence of psoriatic lesions.

Prediction of 30-year cardiovascular disease risk in psoriatic population

In psoriatic population the Framingham risk score (FRS) has been used to assess the risk of major cardiovascular (CV) events for a 10-year follow up period1-6. The established CV risk factors that are significant in models based on shorter follow-up duration are also related to CV disease (CVD) incidence in 30 years7-8. Nowadays, clustering of risk factors at younger ages and increasing life expectancy suggest the need for longer-term risk prediction tools. This article is protected by copyright. All rights reserved.

Serological screening for autoimmune polyendocrine syndromes in patients with vitiligo

Editor Vitiligo is often associated with autoimmune diseases, both systemic and organ-specific, and is also described as a manifestation of the so-called autoimmune polyendocrine syndromes (APSs), which are a combination of autoimmune disorders classified into four groups. Although APSs are rare syndromes, it is possible that their incidence is underestimated because of their ‘incomplete’ presentations with positive autoantibody status only, occasionally associated with an overt major or minor component of the syndrome. In this study, we analysed the association of vitiligo with systemic and organ-specific autoimmune diseases, searching for the presence of serological APSs, the so-called ‘incomplete’ APSs. Serum antibodies were measured in thirty vitiligo patients, 18 men and 12 women, with a mean age of 48.2 years (range: 18–75). Results are summarized in Table 1. The APSs’s study showed in 16 patients (53%) an association between vitiligo and autoimmune-thyroid disorders (APS-3C). In seven (23%) patients, no other combination of disorders was observed. In one (3%) patient, endocrine disorders (APS-3C + A) coexisted. In another (3%) patient, gastrointestinal autoimmune disease (APS-3C + B) coexisted. In addition, in four (13%) patients, collagen diseases ⁄ vasculitis (APS-3C + D) coexisted. Overall, three vitiligo patients had more than one circulating organ-specific or systemic antibody in addition to vitiligo: two patients (7%) presented with APS-3C + A + B and one patient (3%) presented with APS-3C + B + D. Serological associations not included in the other APS subtypes and involving vitiligo (APS-4) were reported in seven (23%) patients (i.e. vitiligo and diabetes mellitus). Seven (23%) patients had vitiligo without any antibodies detected. The goal of the present work was the identification of the pre-clinical phase (potential and latent) of autoimmune diseases associated with vitiligo through a complete antibody panel evaluation. The study of ‘incomplete’ APS demonstrated a characteristic feature of autoimmune disorders, such as the tendency in the same subject for the coexistence of multiple autoimmune diseases which often occur in preferential clusters of association, as in APS. For reasons of high frequency of latent forms of APS, a diagnostic two-step algorithm was developed and used by Amerio et al. for diseases associated with vitiligo. We revised this algorithm in light of our results (Fig. 1). The diagnostic approach used in our study, suggesting a battery of antibodies to be assayed in all patients with vitiligo, corresponds to the first phase of this algorithm. All these patients should have the thyroid antibodies (TPOAb and TgAb) assayed first. Then, the assessment should include the detection of ANA, GPCAb, and GADAb and IA2Ab. The presence of tTGAb and ACAb should be reserved for patients with a high family risk. A recent review on autoimmunity has been recommended to restrict the antibody list to detect the most frequent autoimmune diseases in high-risk populations. On the contrary, we preferred to include those infrequent diseases, such as Addison’s disease, searching for their presence only in specific subjects. Only in the case of an antibody’s positivity is the second phase conducted and is based on the implementation of clinical and

Ulcus vulvae acutum — A case of genital ulcers in adolescent girl

Ulcus vulvae acutum is a rare clinical condition characterized by the presence of multiple acute painful genital ulcers of non-venereal origin associated with systemic symptoms in young women. The aetiopathogenesis of the disease is not fully understood, although recent reports have associated it with the Epstein–Barr virus. Diagnosis is difficult and generally made by exclusion after venereal diseases, and autoimmune, inflammatory, traumatic, and neoplastic causes. We describe a case of adolescent female with an episode of ulcus vulvae acutum associated with infectious mononucleosis. The diagnosis was supported by the clinical symptoms, elevated circulating levels of liver enzymes, positive EBV serology, cervical and inguinal lymphadenomegaly, and hepatosplenomegaly. The patient presented a history of aphthous stomatitis. Negative Pathergy test and the absence of any other related symptoms allowed us to exclude the Behçhet syndrome. Lesions healed with no sequelae or recurrences.

Myocardial Infarction in a Patient Treated with Anti-Interleukin-12 Biological Agent for Chronic Plaque Psoriasis

Dear Editor: We present the case of a 55 year-old woman affected by psoriasis since she was 40 years old. Her personal history reveals hepatic steatosis, hypertension, dyslipidemia, obesity, and gastro-esophageal reflux disease. She had been smoking 8 cigarettes a day for 30 years and she occasionally consumed alcohol. In 2005, she was treated with Cyclosporine, which was stopped after an episode of transient ischemic attack after five months of therapy. In 2009, she started Adalimumab phial 40 mg every 2 weeks for 8 months. About 9 months later, Adalimumab was restarted and stopped after 6 months due to inefficacy. She underwent narrow-band ultraviolet B phototherapy without any clinical benefit; it was therefore decided to start her on Ustekinumab 45 mg fl. The patient performed the first administration of the drug and after six days, she suffered from an acute myocardial infarction. The coronary angiography demonstrated a two-vessel coronary artery disease. It is not possible to absolutely define the relationship between this cardiovascular event and the Ustekinumab intake. While she clearly had several important cardiovascular risk factors, she was never referred for angina. However, the coincidence with the first dose of the biologic drug cannot be overlooked. A pathogenetic hypothesis to explain the possible higher prevalence of major adverse cardiovascular events (MACEs), especially at the start of treatment, might be related to the stabilizer role of interleukin (IL)-17 on the atheromatous plaque1. Nevertheless, the pro-inflammatory effect of Th1 and Th17 cytokines on the plaque development and rupture has been demonstrated; especially, the link between IL-17 and the instable atheromas could sustain the increased risk of acute myocardial infarction in psoriatic patients2. Also, clinical data are controversial: a meta-analysis of pooled data from phase II/III clinical studies on Ustekinumab reported a non-significant difference in the effect of the biological drug on cardiovascular events between the treated psoriatic patients and the placebo group3. Another meta-analyses of randomized controlled trails in psoriatic patients, investigating the association between anti-IL-12/23 agents (Ustekinumab and Briakinumab) and MACEs did not show a significant increase in the risk of MACE, even though 10 events in 3,179 treated patients and 0 events in 1,474 control patients were observed4. On the other hand, a significant difference was reported in the rate of MACEs observed in patients receiving anti-IL-12/23 agents5. Briakinumab and Ustekinumab are both human monoclonal antibodies targeting the same shared sub-unit (p40) of IL-12 and IL-23; a class effect therefore cannot be excluded. However, because Briakinumab is more responsible for major cardiovascular effects than Ustekinumab, it was withdrawn from the market. Our report demonstrates that a single injection of the biologic drug might have promoted a myocardial infarction. Due to the quick interval between the drug intake and the appearance of MACE, we focused our attention on the short term effect rather than the cumulative effect; the literature describes the temporal interval ranges from 2 to 17 weeks (mean: 9,8)3. If meta-analyses have not been able to clarify the issue, it is unlikely that a single report could provide further clarification. However, it is important to maintain awareness of this issue and in the presence of cardiovascular risk factors attention should be taken when using this drug.

Is Scleroderma Pattern Able to Address a Specific Diagnosis of Connective Tissue Diseases

Introduction : Nailfold videocapillaroscopy (NVC) is a non-invasive imaging technique widely used to investigate microvascular abnormalities in different connective tissue diseases (CTDs). Methods : We conducted a retrospective study where we analysed 415 patients submitted to NVC. Patients with scleroderma-like pattern were selected to investigate if there are specific NCV changes, which discriminate among the different CTDs. Ninety-one patients met this requirement and had a diagnosis of CTD. For each patient the following abnormalities were observed: enlarged and giant capillaries, oedema, loss and rarefaction of capillaries, long loops and minor dystrophies. Results : Multivariate analyses did not reveal any specific modification among the analysed co-variables for scleroderma (SS) and dermatomyositis (DM). For the others CTDs analysed in this study, logistic regression revealed that some of the capilloroscopic features could be indicative of specific diseases. Of note, the presence of megacapillaries with long loops in a scleroderma-like pattern seems to be highly indicative for a diagnosis of systemic lupus erythaematosus (SLE). Conclusions : Our data showed that in CTDs with a scleroderma-like pattern, the NVC variables alone are not able to discriminate for a specific diagnosis of CTD. Nevertheless, there are some NVC features, which could strongly address the differential diagnosis toward a specific CTD.