Giovanni Ciancio

Successful treatment of SAPHO syndrome with infliximab: report of two cases

The treatment of SAPHO syndrome is empirical and has recently been reviewed.1–3 Non-steroidal anti-inflammatory drugs (NSAIDs) are the first choice but have limited efficacy. Second line drugs have been tried with mixed results. Positive effects with pamidronate, which partly works by blocking tumour necrosis factor α, have been reported.3,4 Recently, Maksymowych et al suggested that pamidronate is also effective in spondarthritis, which shares manifestations and clinical associations with the SAPHO syndrome.5,6 Infliximab, a chimeric anti-tumour necrosis factor α monoclonal IgG1 antibody, has recently been proved to be effective in the treatment of ankylosing spondylitis7,8 and psoriatic arthritis.7,9 In view of this information we treated two patients affected by refractory SAPHO syndrome with infliximab. Both patients had chest pain limiting normal activity despite adequate treatment with NSAIDs and second line treatment was unsuccessful. Both patients received three intravenous infusions of infliximab (5 mg/kg) at …

Ankylosing spondylitis and undifferentiated spondyloarthropathies: a clinical review and description of a disease subset with older age at onset.

The onset of ankylosing spondylitis, as defined by the currently used criteria, after the age of 50 years is uncommon. Late-onset undifferentiated spondyloarthropathy is relatively more frequent. Its clinical spectrum seems to be as wide as it is in children and young and middle-aged adults. Most patients have two or more manifestations of spondyloarthropathy and meet the Amor criteria or the European Spondylarthropathy Study Group criteria. Some patients show only one manifestation of the B27-associated disease process for years and need more sensitive criteria. A subset of patients shows distal inflammatory swelling with pitting edema on the dorsum of feet or hands together with peripheral arthritis and peripheral enthesitis. In these cases spondyloarthropathy must be differentiated from other inflammatory rheumatic diseases with elderly onset showing the same distal inflammatory swelling with pitting edema.

Inflamed shoulder structures in polymyalgia rheumatica with normal erythrocyte sedimentation rate.

OBJECTIVE To investigate the inflammatory involvement of shoulder articular and extraarticular structures in polymyalgia rheumatica (PMR) patients with a normal erythrocyte sedimentation rate (ESR) at diagnosis. METHODS This was a case-control study. All consecutive, untreated new outpatients diagnosed as having PMR with a normal ESR (<40 mm/hour) during a 6-month period were included in the study (case patients). Controls were 12 consecutive, untreated PMR outpatients with an ESR of >40 mm/hour who were observed after the case patients. Before starting corticosteroid therapy, all case patients and controls underwent bilateral shoulder ultrasonography (US) and magnetic resonance imaging (MRI). US and MRI scans were evaluated independently by two radiologists who were blinded to the reciprocal results. RESULTS Six case patients (4 men and 2 women) and 12 controls (4 men and 8 women) were studied. Both US and MRI demonstrated bilateral subacromial/subdeltoid bursitis in all 6 case patients and in 11 of the 12 (92%) controls (P not significant [NS]). One control had unilateral bursitis. Glenohumeral joint synovitis was found in 4 of 6 case patients (67%) by MRI and in 3 of 6 case patients (50%) by US (P NS), as well as in 8 of 12 controls (67%) by MRI and in 7 of 12 controls (58%) by US (P NS). Both MRI and US detected biceps tenosynovitis in 5 of 6 case patients (83%) and in 8 of 12 controls (67%) (P NS). The severity of bursitis did not differ significantly between the groups. US was as effective as MRI in detecting inflammatory changes of the shoulder. CONCLUSION MRI and US studies showed that PMR patients with normal or high ESRs have similar inflammatory shoulder lesions. Moreover, bilateral subacromial/subdeltoid bursitis represents the imaging hallmark in PMR patients with a high or normal ESR. MRI or US of the shoulder may facilitate the proper diagnosis in patients with the typical proximal symptoms of PMR who also have normal ESRs.

HLA-G may predict the disease course in patients with early rheumatoid arthritis.

The current management of early rheumatoid arthritis (ERA) is to start an intensive treatment as soon as possible. To avoid under/overtreatment, it is important to identify reliable ERA evolution biomarkers. HLA-G molecules has been associated with rheumatoid arthritis, suggesting a role in disease regulation. HLA-G antigens are expressed as membrane bound and soluble isoforms (mHLA-G, sHLA-G) that act as ligand for immune-inhibitory receptors (ILT2, ILT4, KIR2DL4). Expression of HLA-G is influenced by a 14 bp insertion/deletion polymorphism in exon 8 of the gene, where the deletion is associated with mRNA stability. We analyzed 23 ERA patients during a 12 months follow-up disease treatment for sHLA-G, IL-1beta, IL-6, IL-10 and TNF-alpha levels in plasma samples by ELISA, mHLA-G and ILT2 expression on peripheral blood CD14 positive cells by flow cytometry and typed HLA-G 14 bp deletion/insertion polymorphism by Real-Time PCR. Disease status (DAS28), ultrasonography with power Doppler and laboratory data were checked. Cytokine levels confirmed the anti-inflammatory effect of the treatment. sHLA-G, mHLA-G and ILT2 expression inversely correlated with DAS28 disease scores. The frequency of 14 bp deletion allele increased in patients with disease remission. Based on these results, HLA-G may be a candidate biomarker to evaluate early prognosis and disease activity in ERA patients.

The Evolution of Adult-Onset Still Disease: An Observational and Comparative Study in a Cohort of 76 Italian Patients

OBJECTIVES Adult-onset Stills disease (AOSD) is a potentially crippling or life-threatening rare disease that may be self-limited, intermittent, and chronic. Clinical predictors of outcome are still lacking, as is information on the rate of progress of its chronic course. The main objective is to identify factors that improve our ability to predict the course of AOSD, and factors associated with the rate of progress of its chronic course. A comparison with the literature is included. METHODS A retrospective cohort observational study conducted at the tertiary-referral Rheumatology Unit in Ferrara, Italy. RESULTS Seventy-six patients (44 females and 32 males) referred to the Unit and who satisfied the criteria for AOSD were identified. Our findings on white AOSD patients are largely compatible with those previously published. Ferritin level, as well disease activity score (DAS(28)), is associated with the rate of progression of the articular manifestations of the disease. A polyarthritis persisting over 6 months is associated with the development of a chronic articular course, irrespective of the size of the involved joints. CONCLUSIONS Ferritin, being associated with the course of AOSD, could play a role in the diagnosis of the disease. Together with DAS(28), it might also serve as a useful predictor for the rate of progress of the chronic course of the disease, as measured with simple erosion narrowing score.

Combination treatment with etanercept and an intensive spa rehabilitation program in active ankylosing spondylitis.

The aim of this study is to determine the effects of a combination treatment with etanercept and spa rehabilitation versus etanercept alone on function, disability and quality of life in a group of patients with active ankylosing spondylitis (AS). Sixty patients with AS underwent etanercept as suggested by ASAS/EULAR recommendations. As the clinical and laboratory conditions improved, 30 patients accepted the proposal of coupling the medical therapy with a 7-day rehabilitation program in a thermal baths centre; the remaining 30 subjects continued to take the biologic agent alone. The comparisons between the 2 groups were made after 3 and 6 months. The primary outcome was an improvement in BASFI. The secondary outcome was an improvement in the visual analogic scale of EuroQol (EQ-5Dvas). After 6 months a statistically significant improvement in BASFI (p < 0.05) and EQ-5DVAS (p < 0.05) scores was observed in both groups. The mean change in EQ-5DVAS value showed a statistically significant difference in favour of the combination therapy group versus the monotherapy group (22 vs 32, p < 0.05). A therapeutic regimen combining etanercept with an intensive rehabilitation program contributes to disability reduction and ameliorates quality of life for AS patients.

The HLA-B*2709 subtype in a patient with undifferentiated spondarthritis

In 1998, in this journal, we reported the cases of two B27 positive patients with undifferentiated spondyloarthropathy (uSpA) and showing dactylitis also affecting the synovial sheaths in the palm of the hand.1 Neither patient had axial disease but showed peripheral manifestations of spondyloarthropathy (SpA), such as peripheral arthritis, peripheral enthesitis, and dactylitis. Recently, one of our two patients (No 2) was subtyped and found to be B*2709 positive. As far as we know this subtype has never been found in patients with SpA. DNA typing of HLA class I alleles was performed using a DNA sample prepared from peripheral blood lymphocytes by the salting out procedure.2 The class 1 ABC SSP UNITRAY low resolution kit (Pel-Freez) was used. The primer sets amplify all alleles described by the International Nomenclature Committee of WHO in 19953and in …

Epidemiology of gout and chondrocalcinosis

Gout is the most common cause of inflammatory arthritis affecting at least 1% of the population in industrialized countries. It is closely associated with hyperuricemia and is characterized by formation and reversible deposition of monosodium urate crystals in joints and extra-articular tissues. Several studies suggest that the prevalence and incidence of gout are rising. Numerous risk factors may in part explain this increasing trend including dietary and lifestyle changes, genetic factors, diuretic use and comorbid conditions such as hypertension, diabetes, cardiovascular disease, chronic renal disease and the metabolic syndrome. Chondrocalcinosis is characterized by the deposition of calcium pyrophosphate crystals in articular tissues, most commonly fibrocartilage and hyaline cartilage. Sporadic chondrocalcinosis is a common condition in the elderly and frequently associates with osteoarthritis. Hereditary haemochromatosis, hyperparathyroidism and hypomagnesaemia are metabolic disorders that predispose to secondary chondrocalcinosis.The prevalence of chondrocalcinosis is still rather uncertain and varies depending on the diagnostic criterion used in different studies.

Nicotine-patch therapy on mucocutaneous lesions of Behçet’s disease: a case series

OBJECTIVE We report the use of nicotine-patch therapy on active mucocutaneous lesions of Behçets disease (BD). METHODS Five BD ex-smoker patients with refractory active mucocutaneous manifestations were treated with nicotine patches for 6 months. RESULTS Four out of five patients quickly responded to nicotine-patch therapy and experienced a complete regression of mucocutaneous lesions. Other manifestations of BD did not respond and new manifestations appeared during this treatment. One patient had no benefit from therapy but on restarting smoking it was promptly effective. CONCLUSIONS Mucocutaneous lesions associated with BD may be modulated by smoking. Both smoking and nicotine-replacement therapy may be efficacious not only on oral aphthae, but also on other mucocutaneous manifestations, whereas the efficacy in the treatment and prevention of other systemic manifestations of BD is not proven. At least in ex-smokers, nicotine in its pure form is well tolerated and its use could be justified in selected cases of BD with predominant and recurrent refractory mucocutaneous manifestations.

Colour duplex ultrasonography in the management of giant cell arteritis.

The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are generally used in monitoring and tapering glucocorticoid therapy in giant cell arteritis (GCA). However, the acute-phase reactants are useful but not absolute indicators of disease activity [1, 2]. Recently we established the pace of the tapering schedule of a patient with GCA by using color duplex ultrasonography (US). The patient, a 67-year-old-man, came to us with a history of new-onset headache and fatigue. His medical history was otherwise unremarkable. Physical examination showed tenderness and swelling along the left temporal artery. The only aspects of laboratory evaluation worthy of note were an ESR (Westergren) of 55 mm/1st h and a CRP level of 37 mg/l (normal <5). Colour duplex US showed a dark halo of 1.8 mm around the lumen of the frontal ramus of the left temporal artery, together with an abnormal peak-systolic blood-flow velocity. The patient was diagnosed as having GCA and was given prednisone at a dosage of 50 mg/day. One week afterwards ESR and CPR were unchanged, but the dark halo around the lumen of the temporal artery and the peak-systolic blood-flow velocity were reduced by 20% (Fig. 1). As his symptoms had disappeared the tapering of prednisone began and continued over the following 6 months, up to the present dose of 2.5 mg/day. In the second month of therapy the daily dose was only 5 mg. Several studies have emphasized the diagnostic potentialities of color duplex US in GCA [3, 4, 5, 6, 7]. Nevertheless, so far there is no general agreement on the advantages of this method compared with an accurate clinical examination of the temporal arteries. Thus the biopsy remains the gold standard for the diagnosis of GCA [8]. Recently it has been suggested that the dark hypoechogenic halo is strongly related to the acute phase of the disease [9]. By monitoring the halo s thickness and by measuring at the same time the blood-flow velocity in the arteries, we were able to better assess the response to glucocorticoids. These parameters improved and returned to normal earlier than ESR and CRP. Future studies on color duplex US of the temporal artery in GCA should also look at its therapeutic utility.