Efficacy of mud plus bath therapy as compared to bath therapy in osteoarthritis of hands and knees: a pilot single-blinded randomized controlled trial.

The primary objective of this study was to assess the efficacy of mud plus bath therapy in comparison to bath therapy alone in hand and knee osteoarthritis (HOA and KOA). We conducted a single-blinded randomized controlled trial (RCT). Patients were randomly assigned to either mud plus bath therapy (group 1) or balneotherapy (group 2). The primary outcome was a change in AUSCAN questionnaire for HOA and in WOMAC for KOA at month 12. Evaluations were performed at baseline (B), immediately after the interventions (week 2, W2) and after 3 (M3), 6 (M6), 9 (M9) and 12 (M12) months. 37 patients with KOA and 52 with HOA were randomized in the study. In HOA patients, AUSCAN pain improved more in group 1 compared to group 2 at M3, M6 and M12 (p<0.001, p=0.001 and p=0.038, respectively). AUSCAN stiffness improved more in group 1 at M3 (p=0.001). AUSCAN function improved more at M3, M6, M9 and M12 (p=0.001, p=0.001, p=0.014 and p=0.018, respectively). Regarding, KOA, WOMAC function decreased more prominently in group 1 compared to group 2 at M9 (p=0.007). The absolute values of WOMAC function at M6 and M9 were lower in group 1 compared to group 2 (p=0.029 and p=0.001, respectively). WOMAC pain absolute values were lower in group 1 at W2 (p=0.044) and at M9 (p=0.08). We conducted a RCT on the efficacy of mud plus balneotherapy over balneotherapy alone in HOA and KOA. We found that mud plus balneotherapy was more effective than balneotherapy alone on clinical outcomes of HOA. Differences in clinical outcomes of KOA were not significant, yet numerically higher.

Validation of a diagnostic score for the diagnosis of autoinflammatory diseases in adults.

Most autoinflammatory disorders typically come out in the pediatric population, although a limited number of patients may experience disease onset during adulthood. To date, a late disease onset has been described only in familial Mediterranean fever, caused by mutations in the MEFV gene, and in tumor necrosis factor receptor-associated periodic syndrome, caused by mutations in the TNFRSF1A gene. The relative rarity and lack of information on adult-onset autoinflammatory diseases make it likely that mutations will be found in an even smaller percentage of cases. With the aim of improving the genetic diagnosis in adults with suspected autoinflammatory disorders, we recently identified a set of variables related to the probability of detecting gene mutations in MEFV and TNFRSF1A and, in addition, we have also proposed a diagnostic score for identifying those patients at high risk of carrying mutations in these genes. In the present study we evaluated the preliminary score sensitivity and specificity on a wider number of patients in order to validate the goodness of fit of the model. Two hundred and nineteen consecutive patients with a clinical history of periodic fever attacks were screened for mutations in MEFV and TNFRSF1A genes; detailed information about family/personal history and clinical manifestations were also collected. For the validation of the score we considered data both from the 110 patients used to build the preliminary diagnostic score and from the additional 219 patients enrolled in the present study, for a total number of 329 patients. Early age at disease onset, positive family history for recurrent fever episodes, thoracic pain, abdominal pain and skin rash, which are the variables that had previously been shown to be significantly associated with a positive genetic test result (12), were used for validation. On univariate analysis the associations with a positive genetic test were: age at onset (odds ratio [OR] 0.43, p=0.003), positive family history for recurrent fever episodes (OR 5.81, p<0.001), thoracic pain (OR 3.17, p<0.001), abdominal pain (OR 3.80, p<0.001) and skin rash (OR 1.58, p=0.103). The diagnostic score was calculated using the linear combination of the estimated coefficients of the logistic multivariate model (cut-off equals to 0.24) revealing good sensitivity (0.778) and good specificity (0.718). In conclusion, our score may serve in the diagnostic evaluation of adult patients presenting with recurrent fever episodes suspected of having an autoinflammatory disorder, helping identify the few subjects among them who may be carriers of mutations in MEFV and TNFRSF1A genes.

Protein Z G79A and A-13G gene polymorphisms in Italian patients with Behçet's disease.

OBJECTIVE: To investigate potential associations between A-13G and G79A polymorphisms of the protein Z gene and venous thrombosis and other clinical manifestations in Italian patients with Behçet's disease (BD). METHODS: 176 Italian patients who satisfied the International Study Group criteria for BD and 134 healthy age- and sex- matched blood donors were genotyped for A-13G and G79A polymorphisms of the protein Z gene by molecular methods. 113 and 112 of the 176 BD patients were also genotyped for factor V Leiden and prothrombin gene G20210A polymorphisms. Serological HLA class B51 typing was performed by a standard microlymphocytotoxicity technique. The patients were subgrouped according to the presence or absence of clinical manifestations. RESULTS: The distribution of allele and genotype frequencies of A-13G and G79A polymorphisms did not differ significantly between BD patients and healthy controls.The frequencies of carriage rates of protein Z G79A and A-13G polymorphisms in BD patients with and without DVT were similar. Similarly, no associations between thrombotic events and the protein Z gene polymorphisms studied were observed in BD patients carrying factor V Leiden or prothrombin gene G20210A mutations. No significant associations were observed between protein Z polymorphisms and the occurrence of specific clinical findings. CONCLUSION: No association between DVT and A-13G or G79A polymorphisms of the protein Z gene was found in Italian BD patients. Furthermore, these protein Z polymorphisms in BD do not seem to increase the risk of DVT due to factor V Leiden or prothrombin gene G20210A mutations.

Toll-like receptor 4 (TLR4) gene polymorphisms in Italian patients with Behçet's disease.

OBJECTIVE: To investigate potential associations between toll-like receptor 4 (TLR4) gene polymorphisms and susceptibility to, clinical features, and severity of Behçet's disease (BD). METHODS: A total of 189 Italian patients who satisfied the International Study Group criteria for BD and 210 healthy age- and sex-matched blood donors were genotyped for two coding single nucleotide polymorphisms of TLR4 (Asp299Gly and Thr399Ile) by molecular methods. The patients were subgrouped according to the presence or absence of clinical manifestations. Severity score was calculated. RESULTS: The distribution of allele and genotype frequencies did not differ significantly between the BD patients and the healthy controls. No significant associations were found when BD patients with and those without clinical manifestations were compared. No association between TLR4 polymorphisms and severity score was observed. CONCLUSION: Our data suggest that the TLR4 gene polymorphisms are not associated with susceptibility to, clinical expression of, and severity of BD in Italian patients.

Phytothermotherapy: a possible complementary therapy for fibromyalgia patients.

OBJECTIVE: It is a traditional practice in the Alpine region of Trentino and Alto Adige (Italy) to use phytothermotherapeutic treatment with fermenting grass ("hay baths") for rheumatic diseases. However, despite its long history and popularity, a clinical validation of the efficacy and tolerability of the treatment has yet to be found in current literature. Fibromyalgia syndrome (FMS) is characterised by generalised musculoskeletal pain, high tender point counts, sleep disturbance, fatigue, headaches, irritable bowel syndrome, frequent psychological distress and depressed mood. There is no standard therapy regime for FMS and the variety of medical treatments used have given limited benefits. The aim of this study was to assess the efficacy and tolerability of a cycle of phytothermotherapy through a single-blind, controlled, randomised trial, in patients with primary FMS. METHODS: Fifty-six patients with primary FMS according to the ACR criteria were randomly allocated to two groups: 30 were submitted to phytothermotherapy at the thermal resort of Garniga Terme (Trento, Italy) and the other 26 were considered as controls. All patients were evaluated by FIQ, Tender Points Count, HAQ and AIMS1 at baseline, after 10 days, then after 12 and 24 weeks. RESULTS: Patients submitted to phytothermotherapy showed visible and significant improvement of all evaluation parameters at the end of the treatment, which persisted during the follow-up period. No significant difference was found in the control group. Regarding the tolerability, none of the patients presented side effects. CONCLUSIONS: Our results suggest the efficacy and the tolerability of phytothermotherapy in patients with primary FMS.

[Phytothermotherapy with fermenting alpine grass in knee osteoarthritis: mid-long term results]. / Fitobalneoterapia con bagni nell'erba di montagna in fermentazione nella gonartrosi: risultati a medio-lungo termine.

This is an observational study of the mid-long-term results of a single course of phytothermotherapy with grass baths (group A, 54 patients), of a course of usual medical care (group B, 58 patients) and of a course of physiokinesistherapy (FKT, group C, 30 patients) in knee osteoarthritis. For each group of consecutively treated patients we evaluated the Lequesne algo-functional Index, the drug consumption, the frequency of the patient-physician contacts and laboratory or radiological examinations after 10-15 days of treatment and at 3, 6, 9 and 12 months with blind telephonic follow-up. The mean Lequesne-score at basal time was 7.5+/-3.3, 11.9+/-5.3 and 11.0+/-2.7 in group A, B and C respectively. In each group this score diminished at the end of the treatment (p<0.001). At 3, 6, 9 and 12 months the score remained lower than at basal time in group A (p<0.001) and group B (p<0.01), but not in group C. Drug consumption, patient-physician contacts and lab examinations were 5 times lower in group A than in group B and group C at basal time and throughout the follow-up. The study underlines the mid-long term efficacy of grass baths on both pain and functionality in knee osteoarthritis; this effect, compared to basal values, was even more evident at 3 and 6 months than that of usual medical care. FKT shows improvement only at the end of the treatment, but not long-lastingly.

Lack of association of the -463 G/A myeloperoxidase promoter polymorphism with Behcet's disease in Italian patients.

OBJECTIVE: To investigate potential associations between the -463 G/A myeloperoxidase (MPO) promoter polymorphism and susceptibility to, and clinical expression of, Behçet's disease (BD). METHODS: One hundred and seventy-five Italian patients who satisfied the International Study Group criteria for BD and 235 healthy age- and sex-matched blood donors were genotyped for the -463 G/A promoter polymorphism of the MPO gene by molecular methods. The patients were subgrouped according to the presence or absence of clinical manifestations. RESULTS: The distribution of allele and genotype frequencies of the MPO -463A/G polymorphism did not differ significantly between the BD patients and the healthy controls. Carriers of the -463 A allele (A/A or A/G) [odds ratio (OR) 0.7, 95% confidence interval (CI) 0.5-1.1] and homozygosity for A allele (OR 0.3, 95% CI 0.1-1.3) were less frequent among BD patients than among the controls, but the difference was not statistically significant. No significant associations were found when BD patients with and those without clinical manifestations were compared. CONCLUSION: Our data suggest that the -463 G/A promoter polymorphism of the MPO gene is not associated with susceptibility to, and clinical expression of, BD in Italian patients.

Clinical manifestations of Behçet's disease in 137 Italian patients: results of a multicenter study.

OBJECTIVE: To determine the type and frequency of clinical features of Behçet's disease in a population of Italian patients. METHODS: We retrospectively studied 137 Italian patients (76 males and 61 females, age at onset 29.6 +/- 12.2 [mean +/- SD] years) seen consecutively in nine different referral centers. The duration of follow-up at study entry was 10.9 +/- 8.2 years. Virtually all patients fulfilled the classification criteria developed by the International Study Group for Behçet's disease. The clinical manifestations of the patients were recorded by the attending physicians using specifically designed forms. RESULTS: The most frequent manifestations at disease onset were oral (78.3%) and genital aphthae (29.2%) followed by inflammatory ocular involvement (20%) and arthritis (14.2%). The commonest (>50% of cases) manifestations observed throughout the disease course were oral aphthae (99.3%), genital aphthae (62.8%), various cutaneous lesions including erythema nodosum (81.8%), and inflammatory ocular disease (60.6%). Panuveitis and posterior uveitis/retinitis occurred more frequently in males compared with females (28.9% versus 11.5% and 57.9% versus 36.1%, respectively; p < 0.05). 61.6% of our patients were HLA-B51 positive. CONCLUSION: Behçet's disease in Italian patients is characterized by a variety of clinical manifestations in agreement with the medical literature. Panuveitis and posterior uveitis/retinitis occur more frequently in male patients.

Association of MICA alleles and HLA-B51 in Italian patients with Behçet's disease.

OBJECTIVE: To evaluate the distribution of the MHC class I chain related gene A transmembrane (MICA-TM) alleles in Italian patients with Behçet's disease (BD), and to investigate the relative contribution of MICA alleles and HLA-B51 in the susceptibility and specific clinical features of BD. METHODS: A total of 69 consecutive Italian patients who satisfied the International Study Group criteria for BD were followed at rheumatology, ophthalmology, and neurology units during a 3 year period (1997-99). We selected 130 healthy subjects from the same geographic areas as controls. All patients and controls were examined for MICA microsatellite polymorphisms using polymerase chain reaction. Serological HLA class B51 typing was performed by a standard microlymphocytotoxicity technique. RESULTS: A strong association with HLA-B51 was observed in patients with BD (OR 5.7, 95% CI 2.8-11.3). The MICA-TM allele A6, in linkage disequilibrium with HLA-B51, was only slightly increased in patients compared to controls (60.9% vs 50.8%; p = NS). No significant associations between HLA-B51 or MICA-TM alleles and clinical subgroups, particularly central nervous system or eye involvement, were found. CONCLUSION: HLA-B51 is the most important susceptibility gene in BD. Association with MICA-A6, when it exists, is secondary to the strong linkage disequilibrium with HLA-B51.

Intercellular adhesion molecule-1 gene polymorphisms in Behçet's Disease.

OBJECTIVE: Intercellular adhesion molecule 1 (ICAM-1) is strongly expressed in vascular endothelial cells and perivascular inflammatory infiltrates in immunopathologic studies of Behçet's disease (BD) lesions. ICAM-1 genes may contribute to the inflammatory events responsible for the vessel damage in BD. We examined potential associations of ICAM-1 gene polymorphisms with BD susceptibility. METHODS: Case patients were 74 consecutive Italian patients with BD who were followed at the Bologna, Ferrara, Milano, Potenza, Prato, Reggio Emilia, and Trento rheumatology, ophthalmology, and neurology units over a 3 year period (1997-99) who satisfied the International Study Group criteria for BD; 228 healthy Italian blood donors from the same geographic areas were selected as control groups. All BD patients and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for ICAM-1 polymorphisms at codon 241 (exon 4) and codon 469 (exon 6). RESULTS: The frequency of R241 was significantly higher in BD patients than in controls (20.3% vs 5.7%; p = 0.001, pcorr = 0.002, OR 4.2, 95% CI 1.9-9.3). The distribution of E/K 469 genotype was similar in patients and controls. Comparing patients with different clinical features, we found only a trend to higher frequency of R241 in patients with articular manifestations (21.4% vs 12.5%; p = 0.08). CONCLUSION: Our findings show that G/R 241 polymorphism of ICAM-1 is associated with BD susceptibility.