Coeliac disease is a risk factor for the development of seronegative arthritis in patients with autoimmune thyroid disease.

OBJECTIVE: Hashimoto's thyroiditis is known to cluster with other systemic autoimmune disorders. Rheumatic manifestations, such as a seronegative non-erosive polyarthritis have been described. The aim of this study was to evaluate the characteristics and the prevalence of rheumatic features in thyroiditis patients, and to ascertain whether the association with systemic autoimmune disorders improved the arthritis manifestations. METHODS: In total, 180 thyroiditis patients were enrolled. Major clinical and demographic characteristics have been recorded. Patients underwent a rheumatological clinical assessment and extra-articular manifestations allowing for a differential diagnosis with systemic autoimmune diseases and spondyloarthropathy. Presence of systemic autoimmune diseases was recorded. RESULTS: A total of 8.33% of thyroiditis patients shown a peripheral inflammatory arthritis (P = 0.002). Female gender (P = 0.042) and thyroid peroxidase (TPOAbs) positivity (P = 0.001) were more frequent. In total, 37 patients had systemic autoimmune diseases (P = 0.0003). A significant high prevalence of coeliac disease and Addison disease was found (P = 0.034 and P = 0.049, respectively). In patients with coeliac disease, the articular manifestations were more frequent (21.21%) (P = 0.001) and the risk to develop joint involvement was 2.96. CONCLUSION: Although we found an articular involvement in about one-third of thyroiditis patients, the prevalence of inflammatory arthropathy was only 8.33%. The prevalence of other coexisting autoimmune disorders was 34.26% with a significant prevalence of coeliac disease (7.41%). Thyroiditis patients with coeliac disease have an articular involvement more frequently than those without. In these patients, we have found a high risk of developing arthritis than patients with only thyroiditis, suggesting cumulative autoimmune effects in the developing articular involvement.

May the analysis of 1918 influenza pandemic give hints to imagine the possible magnitude of Corona Virus Disease-2019 (COVID-19)?

BACKGROUND: In 1918 an unknown infectious agent spread around the world infecting over one-third of the general population and killing almost 50 million people. Many countries were at war, the First World War. Since Spain was a neutral country and Spanish press could report about the infection without censorship, this condition is commonly remembered as "Spanish influenza". This review examines several aspects during the 1918 influenza pandemic to bring out evidences which might be useful to imagine the possible magnitude of the present coronavirus disease 2019 (COVID-19). METHODS: In the first part of this review we will examine the origin of the SARS-Coronavirus-2 and 1918 Spanish Influenza Virus and the role played by host and environment in its diffusion. We will also include in our analysis an evaluation of different approaches utilized to restrain the spread of pandemic and to treat infected patients. In the second part, we will try to imagine the magnitude of the present COVID-19 pandemic and the possible measures able to restrain in the present environment its spread. RESULTS: Several factors characterize the outcome in a viral pandemic infection. They include the complete knowledge of the virus, the complete knowledge of the host and of the environment where the host lives and the pandemic develops. CONCLUSION: By comparing the situation seen in 1918 with the current one, we are now in a more favourable position. The experience of the past teaches us that their success is linked to a rapid, constant and lasting application. Then, rather than coercion, awareness of the need to observe such prevention measures works better.

Quantitative Ultrasound of Proximal Phalanxes in Childhood Acute Lymphoblastic Leukemia Survivors.

Reduced bone mineral density (BMD) is a well-known complication in childhood acute lymphoblastic leukemia (ALL) survivors; the optimal method to assess BMD is still debated. We studied BMD by quantitative ultrasound (QUS) in 72 ALL survivors, and evaluated any correlation with cumulative doses of steroids and cytotoxic agents. Mean age at diagnosis was 61±45 months, while mean age at QUS was 318.3±129.6 months; mean period of follow-up was 41.2±37.8 months. Mean amplitude-dependent speed of sound z-score was -1.22±1.19. Ten survivors (13.8%) presented a z-score below -2 SD. A negative correlation was found between amplitude-dependent speed of sound z-score and age at diagnosis (P=0.01). A positive correlation was observed with length of follow-up (P=0.01). No correlation was found with cytotoxic drugs. This study represents the largest cohort of childhood ALL survivors studied by QUS. Our results suggest that QUS for its characteristics of being radiation free may be an effective option to assess BMD in pediatric age. In addition, our data outline the importance to improve the awareness about the specific expression of this complication in the pediatric age, concerning the major determinants of bone impairment, which are the disease itself and the phase of bone growth when the disease occurs.

Emerging drugs for psoriatic arthritis.

INTRODUCTION: The majority of Psoriatic Arthritis patients experience a good clinical response to anti-Tumor Necrosis Factor (TNF)-α therapies. However, treatment failure with anti-TNF-α can represent a relevant clinical problem. AREAS COVERED: We review the efficacy and safety profile of biological therapies that have been reported from randomized, controlled trials in phase II and phase III available in Pubmed Database for agents targeting IL-12/23p40 antibody (ustekinumab) and IL-17 (secukinumab), inhibitor of phosphodiesterase 4, (apremilast), and of JAK/STAT pathways (tofacitinib) and CTLA4 co-stimulation (abatacept) in Psoriatic Arthritis. EXPERT OPINION: In Psoriatic Arthritis, main emerging drugs are represented by the fully human monoclonal IL-12/23p40 antibody, ustekinumab, the agent targeting IL-17, secukinumab, and the inhibitor of phosphodiesterase 4, apremilast. Results on T cell co-stimulation inhibition by abatacept are insufficient both in psoriasis and in PsA. In vitro investigations on JAK/STAT pathways in PsA suggest that tofacitinib could represent a further valuable therapeutic option. Emerging biological treatments other than anti-TNF agents, ustekinumab, secukinumab and apremilast appear promising for Psoriatic Arthritis and recent studies have showed a good efficacy and an acceptable safety profile; however, further and long-term studies are advocated.

Influenza vaccine with adjuvant on disease activity in psoriatic arthritis patients under anti-TNF-α therapy.

OBJECTIVES: To evaluate the effects on disease activity of seasonal influenza vaccination with adjuvant in psoriatic arthritis (PsA) patients in stable disease activity on anti-TNF-α drugs as compared to not vaccinated PsA patients adequately matched. METHODS: An observational study was conducted on a cohort of PsA patients in stable disease activity who underwent administration of an adjuvanted vaccine for seasonal influenza. Cases (Group 1) were matched for age, sex, disease activity and therapy with not vaccinated PsA patients (Group 2). Analysis included patients data before vaccination (T0), and one month (T1) and three months (T3) after administration of the vaccination for Group 1 and at correspondent intervals for Group 2. Assessment of disease activity parameters was performed at each visit. RESULTS: Twenty-five vaccinated and 25 not vaccinated patients were included in the study. As a first approach, we analysed the data within groups. At T1, as compared to baseline, the group of vaccinated patients had a statistically significant increase in TJC (tender joint count) and ESR (erythrocyte sedimentation rate). At T3, a statistically significant difference from baseline characteristics was found only for the TJC. In Group 2, all the observed variables showed no significant differences when comparing baseline to T1 and T3. Analysis of the data between groups at T1, Group 1, as compared to Group 2, showed a significant increase of TJC, ESR, HAQ (Health Assessment Questionnaire), PtGA (patient global assessment) and PhGA (physician global assessment). These findings were also confirmed when comparing the two groups at T3 for ESR and PtGA, while they were not confirmed for TJC, HAQ and PhGA. CONCLUSIONS: Influenza vaccination is clinically efficacious in PsA patients under anti-TNF-α therapy, but it could trigger a short-lasting exacerbation of the disease.

Dactylitis in enteropathic spondyloarthritis.

OBJECTIVES: Dactylitis has long been recognised as one of the significant features of spondyloarthropathies. In the literature, the prevalence of dactylitis in enteropathic spondyloarthritis (EASpA) ranges between 2% and 4%. The aim of this study was to identify the prevalence of dactylitis in EASpA patients and to investigate its association with clinical subset and with articular and bowel disease activity. METHODS: 78 EASpA patients and 78 controls were enrolled for this study. All patients and controls underwent a rheumatological and a gastroenterological clinical examination. Demographic and clinical features were recorded. Diagnosis of dactylitis was made by physical examination and was evaluated using the Leeds Dactylitis Instrument (LDI). RESULTS: In our study the prevalence of dactylitis in EASpA was 15.38%, mainly in patients with Crohn's disease (CD) and peripheral arthritis. A significantly higher articular and bowel disease activity was found in patients with dactylitis compared to those without it. The family history of psoriasis represented a predictor of occurrence of dactylitis. Finally, a significant correlation between disease activity and LDI score was found in EASpA. CONCLUSIONS: The results of our study showed a high prevalence of dactylitis in EASpA. It was more frequent in patients with CD and peripheral involvement with a higher articular disease activity, confirming that dactylitis may be a severity marker and a prognostic factor for EASpA. The significant correlation between disease activity and LDI score could address LDI as a potential tool of assessment of dactylitis.

Mud-bath therapy and oral glucosamine sulfate in patients with knee osteoarthritis: a randomized, controlled, crossover study.

OBJECTIVES: To evaluate the efficacy and safety of combined treatment of mud-bath therapy and glucosamine crystalline sulfate (GlcN-S) in patients with knee osteoarthritis (OA). METHODS: This study was a randomised, controlled, crossover investigation. Patients were randomly assigned (1:1) by the investigators to two groups, named group 1 and 2. Group 1 included twenty-three patients receiving oral GlcN-S treatment from the beginning of the study (T0) to the end of the 3rd month of treatment (T3) and a combined treatment of both mud-bath therapy and GlcN-S from T3 to the end of the study at six months (T6). Group 2 included twenty-two patients receiving a combined treatment of both mud-bath therapy and GlcN-S from T0 to T3 and that discontinued mud-bath therapy, receiving GlcN-S treatment alone, from T3 to T6. Primary endpoints of the study consisted of evaluating OA severity and activity at baseline and at follow-up visits. RESULTS: All 45 patients, eligible for the study, completed the period of the crossover. In group 1, no significant difference was shown in the comparison from T0 to T3, while from T3 to T6 most variables were significantly improved. In group 2, instead, the comparison between T0 and T3 showed a significant difference in different parameters. When comparing T3 and T6, despite an improvement of all the variables, no significant difference was shown. CONCLUSIONS: The association of GlcN-S and mud-bath therapy has a positive and safe role in improving pain, function and quality of life in knee OA patients.

Effects of tumor necrosis factor-α inhibitors in mothers and daughters concordant for HLA-B27-positive ankylosing spondylitis.

OBJECTIVES: Pharmacogenomics is considered as the new frontier to predict the response to treatments and it can also be based on the comparison of family members being treated for the same condition. No data are available on the impact of anti-tumour necrosis factor (TNF)-α therapies in members of the same family with ankylosing spondylitis (AS). METHODS: We describe three mother-daughter couples concordant for AS and HLA-B27, both treated with TNF-α inhibitors, for whom the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), and Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP were evaluated during a follow-up of 24 months. RESULTS: All patients manifested improvements of all scores, but the daughters had a more prominent effect achieving faster complete disease remission. CONCLUSIONS: We hypothesise that longer standing chronic inflammation and older age may cause a less prompt and effective response to treatment in SA when compared with their genetically related controls.

Psoriatic Disease: Clinical Staging.

In 2006, the introduction of the concept "psoriatic disease" (PsD) extended the traditional idea of a condition confined to skin and joints. Now we consider PsD a systemic condition, in which the increased activity of tumor necrosis factor acts as the most potent engine for a series of molecular interactions. These lead not only to the genesis of skin and joint symptoms, but also to other clinical aspects such as inflammatory bowel disease, eye involvement, and metabolic syndrome. The blocking of a precise molecular target has dramatically modified therapeutic strategies, making possible adequate control of all the clinical aspects of the condition. Therefore, an expanded clinical staging of patients could now be considered in order to ensure the best therapeutic approach and prognosis.

Fragility Fractures in Patients with Psoriatic Arthritis.

Psoriatic arthritis (PsA) can have peculiar effects on bone, including mechanisms of bone loss such as erosions, but also of bone formation, such as ankylosis or periostitis. The aim of the present study was to describe the prevalence of fractures in patients with PsA as compared to healthy controls and to investigate determinants of fractures among cases. For both cases and controls, radiographs were read to identify vertebral fractures (VF), and the presence of femoral neck or other nonvertebral fractures was obtained from patients' medical history. The prevalence of fragility fractures on radiographic readings did not differ between cases and controls. The number of subjects showing a VF was 33 (36%) among PsA patients and 36 (36%) among controls, with a prevalence of severe VF of 8% among cases and 4% among controls. Controlling for covariates in a logistic model, the only variables showing a significant correlation with the presence of nonvertebral fractures (NVF) were disease duration (p=0.02), age (p=0.03), and bone mineral density at femoral neck (inverse correlation, p=0.04). Fractures should be carefully considered when evaluating the global picture of the patient with PsA for their contribution to the "fragility" profile.

Thalassemic trait prevalence in patients affected by psoriatic arthritis in anti-TNF treatment.

Thalassemic trait (Thal) is associated with rheumatic disease, particularly a mild form of seronegative polyarthritis resembling rheumatoid arthritis (RA), but not with other rheumatic diseases. The aim of this study was to estimate the frequency of Thal in patients with psoriatic arthritis (PsA) and to evaluate the efficacy of anti-tumor necrosis factor alpha (TNF-α) therapy in patients with PsA and Thal. We performed a retrospective study in 321 patients with PsA who started therapy with TNF-α blockers. For all patients included in the study, at baseline and every 3 months for the 1 year of follow up, data concerning PsA activity and ferritin levels were registered. In our group of PsA patients, a total of 27 (8%) with concomitant Thal were identified and included in the study. In patients without Thal, all variables improved significantly after 6 months of therapy, while in patients with Thal, the same variables showed a significant decrease after 12 months.: Our study shows that PsA is significantly associated with Thal, but further studies are needed to address this issue. The presence of Thal could be a negative predictor of achieving remission during treatment with TNF-α-blockers.

The occurrence of lower limb enthesopathy in coeliac disease patients without clinical signs of articular involvement.

OBJECTIVE: Coeliac disease (CD) is a systemic autoimmune condition induced by gluten consumption in genetically predisposed people, affecting ∼1% of the general population. In the literature, there are many studies that report the association between CD and different kinds of arthritis. The aim of this study was to investigate the presence of entheseal abnormalities by US in patients with CD without clinical signs of articular involvement as compared with healthy control subjects. METHODS: Sixty patients with CD attending the gastroenterology outpatient clinic of the University Federico II of Naples and 60 healthy control subjects matched for age and sex were enrolled in this study. Coeliac patients and healthy controls underwent clinical and US examination. RESULTS: Among 60 CD patients, 24 (40%) presented at least one entheseal alteration as compared with 6 (10%) control subjects (P < 0.01). In CD patients, the entheseal site more frequently involved was patellar (distal and proximal), while in the healthy controls the enthesopathies were all localized at the Achilles tendon. CONCLUSION: In conclusion, the results of this study underline the ability of US to detect signs of subclinical enthesopathy and indicate the presence of a higher prevalence of subclinical enthesopathies in asymptomatic CD patients.

Calcium and vitamin D intakes in children: a randomized controlled trial.

BACKGROUND: Calcium (Ca(2+)) and vitamin D (VitD) play an important role in child health. We evaluated the daily intake of Ca(2+) and VitD in healthy children. Moreover, we demonstrate the efficacy of Ca(2+) and VitD supplementation. METHODS: Daily Ca(2+) and VitD intake was evaluated in consecutive healthy children through a validated questionnaire. Subjects with <70% of dietary reference intakes (DRIs) of Ca(2+) and VitD were invited to participate in a prospective randomized trial with 2 groups of nutritional intervention: Group 1, dietary counseling aiming to optimize daily Ca(2+) and VitD intake plus administration of a commercially available Ca(2+) and VitD supplementation product; Group 2, dietary counseling alone. At the enrollment (T0) and after 4 months (T1) serum 25(OH) Vitamin D levels were assessed. RESULTS: We evaluated 150 healthy children (male 50%, mean age 10 years); at baseline a low VitD intake was observed in all subjects (median 0.79 µg/die, IQR 1.78; range 0.01-5.02); this condition was associated with Ca(2+) intake <70% of the DRIs in 82 subjects (55%). At baseline serum 25(OH)D levels were low (<30 ng/ml) in all study subjects and after 4 months of nutritional intervention, a normalization of serum 25(OH)D levels (≥30 ng/ml) was observed in all children in Group 1 and in only one subject in Group 2 [Group 1: T1 33.8 ng/ml (IQR 2.5) vs Group 2: T1 24.5 ng/ml (IQR 5.2), p <0.001]. CONCLUSIONS: Adequate Ca(2+) and VitD intakes are difficult to obtain through dietary counseling alone in pediatric subjects. Oral supplementation with of Ca(2+) and VitD is a reliable strategy to prevent this condition. TRIAL REGISTRATION: The study was registered in Clinical Trials Protocol Registration System (ID number: NCT01638494).

[The complex interplay between health services administration, health professionals and patients. A challenge to take up]. / Azienda sanitaria, operatore di salute, paziente. Una interazione complessa, una sfida da raccogliere.

The risk of loss of essential elements of our professionalism, such as sense of duty, altruism and collegiality, contributes to the difficulties in the interplay between health services administration, health professionals and patients. It is not enough to increase salaries or change organization models. It is also insufficient a generic reference to the values of our profession, but it is mandatory to overcome the self-referencing attitude of health professions.

Effects of antiepileptic therapy on bone mineral status evaluated by phalangeal quantitative ultrasound in pediatric patients with epilepsy and motor impairment.

BACKGROUND: In epileptic patients with motor disability, it's difficult to disentangle the effects of antiepileptic drugs (AEDs) on bone health from those provoked by impaired mobility. The aim of this study was to evaluate the effects of AEDs on bone mineral status by phalangeal quantitative ultrasound (QUS), a no-radiation and non-invasive method, in pediatric patients with motor impairment and epilepsy. METHODS: We enrolled 56 patients (31 females, 25 males) with epilepsy and motor impairment and 24 children with only motor disability (13 females, 11 males). Patients were stratified by Gross Motor Function Classification System Scale (GMFCS) in 4 groups: group A1 with epilepsy and mild motor impairment (GMFCS levels I-II), group A2 with only mild motor impairment, group B1 with epilepsy and severe motor impairment (GMFCS levels III-V), group B2 with only severe motor impairment. The bone mineral status was evaluated by phalangeal QUS and amplitude-dependent speed of sound (AD-SoS) Z-score was calculated for each patient. RESULTS: The four groups showed no significant differences in age, gender and 25-hydroxyvitamin D levels. The group B1 had a statistically lower amplitude-dependent speed of sound Z-score as compared to group A2 (P<0.05). The multivariate analysis of independent factors revealed a significant correlation between amplitude-dependent speed of sound Z-score and Gross Motor Function Classification System levels (P=0.004). The mean Z-score value decreased by 0.53, increasing the motor impairment. CONCLUSIONS: The bone mineral status measured as AD-SoS strongly correlates with severity of motor disability evaluated by GMFCS as compared to antiepileptic therapy and 25-hydroxyvitamin D levels.