Antonio Furlan

Clinical and genetic aspects of Blau syndrome: A 25-year follow-up of one family and a literature review

Blau syndrome (BS) is a rare familial disease transmitted as an autosomal dominant trait, characterized by arthritis, uveitis, skin rash and granulomatous inflammation. Until now BS has been observed in 136 persons belonging to 28 families as well as in 4 sporadic cases. The gene responsible for BS has recently been identified in the nucleotide-binding domain (NBD) of caspase recruitment domain (CARD15/NOD2), also involved in the pathogenesis of Crohns disease. In addition to three missense mutations (R334Q, R334W and L469F) previously identified, a new CARD 15 mutation (E383K) has recently been described in a family followed by us for the past 25 years. The characteristics of this family which, to our knowledge, is the only one affected with BS in Italy, are the object of this manuscript. Both the proband and her daughter were originally affected with a papulonodular skin eruption and then with mild arthritis of the hands and feet. The proband, but not the daughter, complained of severe chronic bilateral uveitis, followed by glaucoma and, a few years later, by cataracts. Histological examination of skin biopsies from both subjects and a joint biopsy (daughter only), showed non-caseating granulomas with multinucleated giant cells which, at electron microscopy, revealed comma-shaped bodies in epithelioid cells, thought to be a marker for BS. The disease is presently well controlled with low doses of prednisone for the mother and non-steroidal anti-inflammatory drugs (NSAIDs) plus low doses of prednisone, when necessary, for the daughter. As in Crohns disease, CARD15/NOD2 mutation is believed to be responsible for the granulomatous autoinflammatory reactions probably triggered by microorganisms in BS.

Elderly onset of primary Sjögren’s syndrome: Clinical manifestations, serological features and oral/ocular diagnostic tests. Comparison with adult and young onset of the disease in a cohort of 336 Italian patients

OBJECTIVESnTo study and compare the clinical and serological features of patients with elderly versus adult and younger onset of primary Sjögrens syndrome (pSS).nnnMETHODSnWe analyzed retrospectively 336 consecutive pSS patients followed at our unit. They were subdivided into three groups according to the age at disease onset: elderly (>65 years), adult (>40 and ≤65 years), and young (≤40 years). Clinical and immunological features of the disease, labial salivary glands biopsy, ocular and oral tests were collected at time of diagnosis and then compared among the three groups.nnnRESULTSnIn 21 (6%) patients, disease onset occurred after the age of 65 years. At the time of diagnosis, 15 (71.4%) of these patients reported symptoms of dry mouth and 16 (76.1%) of dry eye. The most common extraglandular manifestation were arthralgias in 14 (66.7%), Raynauds phenomenon in five (23.8%) and purpura in three (14.2%) cases. Ocular diagnostic tests (Schirmers I and Rose-Bengal staining) were positive respectively in 17 (80%) and nine (44.4%) patients. In eight (38%) cases, unstimulated whole salivary flow showed normal values, while 12 patients (57.1%) showed positivity for salivary sialography. A focus score greater or equal to 1 per 4mm(2) was demonstrated in 11 (53.3%) of the 21 cases.nnnCONCLUSIONnElderly onset of pSS was associated with similar incidence of the diagnostic tests positivity (parotid sialography, ocular tests, minor salivary gland biopsy) in comparison with adult and younger onset. Moreover, no statistical differences were found among the three groups concerning sex, disease duration, as well as ocular and oral symptoms.

The Tumor Necrosis Factor-alpha-blocking Agent Infliximab Inhibits Interleukin 1 beta (IL-1 beta) and IL-6 Gene Expression in Human Osteoblastic Cells

Objective. Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine involved in the pathogenesis of several rheumatic diseases, including rheumatoid arthritis (RA), associated with systemic bone loss and subchondral bone erosions. TNF-α-blocking agents such as infliximab have been successful in treatment of disease-modifying antirheumatic drug-resistant rheumatic diseases. Infliximab therapy in RA also had beneficial effects on local bone destruction and bone mineral density. We assessed effects of infliximab treatment on the bone tissue compartment and cytokine profile expression in vitro. Methods. Osteoblast-like cells were exposed for 24 h to sera of RA patients collected at baseline and after 1 month (T1) and 3 years (T2) of infliximab treatment. Total RNA was extracted, and expression of interleukin 1ß (IL-1ß), IL-6, and osteoprotegerin (OPG) was measured by RT-PCR. Results. IL-1ß gene expression was significantly reduced by the T1 serum, and the same decrease was elicited by the T2 serum. IL-6 downregulation was evident with the T2 serum. OPG was unaffected. Conclusion. The finding of downregulation of inflammatory cytokines was interesting, particularly IL-6, which plays a crucial role in arthritis-related bone loss due to its involvement in osteoclast recruitment and activation. These results may represent a biological explanation and a link for the clinical observation of the beneficial effects of anti-TNF-α agents on the progression of rheumatic diseases at the bone level.

The thickening of flexor tendons pulleys: a useful ultrasonographical sign in the diagnosis of psoriatic arthritis

PurposeTo investigate the frequency of thickening of pulleys for flexor tendons in patients with early arthritis in their hands, and to evaluate it as a predictive sign of PsA.MethodsA prospective observational study involving 228 consecutive patients presenting with recent onset of arthritis in their hands was conducted at rheumatology outpatient clinics in the Veneto region of Italy between October 2014 and September 2017. Diabetic patients were excluded because of the high frequency of trigger finger. The final diagnosis of the rheumatologist delivered after 12xa0months of follow-up, was considered as the gold standard for the analysis of diagnostic accuracy.ResultsTwenty-two patients were excluded from the study because of diabetes. A total of 86 patients with thickening of A1 pulleys in flexor tendons and 120 without were evaluated. Pulley thickness was significantly associated with a family history of psoriasis (18/86 vs 3/120, pxa0˂xa00.001) and diabetes (9/86 vs 4/120, pu2009=u20090.036), and with a personal history of cutaneous psoriasis (25/86 vs 10/120, pxa0˂xa00.001), psoriatic onychopathy (7/86 vs 2/120, pu2009=u20090.028), lower back pain (22/86 vs 11/120, pu2009=u20090.001), Dupuytren’s disease (7/86 vs 2/120 pu2009=u20090.028) and De Quervain tenosynovitis (4/86 vs 0/120, pu2009=u20090.028). In isolation, this sign had a good sensitivity rate (80%). The specificity rate for the disease was barely significative (71%), with an LR+ of 2.71 for PsA.ConclusionsThe thickening of the pulleys in the flexor tendons is an easy-to-detect sign with good sensitivity for the diagnosis of PsA. Its specificity and positive predictive value are not very high; however, if it is included in a complete classification process, sonographers should report it during hand evaluations of patients with arthritis.SommarioScopoStudiare la frequenza di ispessimento delle pulegge tendinee A1 (A1P) dei muscoli flessori delle dita in pazienti affetti da artrite della mano in fase precoce e valutarlo come un segno predittivo di Artrite Psoriasica (AP).MetodiUno studio prospettico osservazionale multicentrico su 228 pazienti ambulatoriali consecutivi che presentavano recente insorgenza di artrite alle mani tra ottobre 2014 e settembre 2017. I pazienti diabetici sono stati esclusi a causa dell’alta frequenza di dito a scatto. La diagnosi finale del Reumatologo Curante dopo un follow-up di 12 mesi è stata confrontata come Gold Standard.RisultatiUn totale di 86 pazienti con ispessimento delle A1P e 120 senza sono stati arruolati. L’ispessimento delle A1P era significativamente associato a storia familiare di psoriasi (18/86 vs 3/120, pxa0˂xa00.001) e di diabete (9/86 vs 4/120, pu2009=u20090.036), con storia personale di psoriasi cutanea (25/86 vs 10/120, pxa0˂xa00.001), di onicopatia psoriasica (7/86 vs 2/120, pu2009=u20090,028), di lombalgia (22/86 vs 11/120, pu2009=u20090,001), di malattia di Dupuytren (7/86 vs 2/120 pu2009=u20090,028) e di tenosinovite di De Quervain (4/86 vs 0/120, pu2009=u20090,028). Isolato, questo segno ha dimostrato una buona sensibilità (80%) per la diagnosi di AP; la specificità per AP era appena significativa (71%) con una LR+ di 2,71.ConclusioniL’ispessimento delle A1P è facile da individuare con una buona sensibilità per la diagnosi di AP. La specificità e il VPP non erano molto elevati. Tuttavia, lo studio ecografico delle pulegge tendinee dovrebbe essere incluso nel processo diagnostico di pazienti con artrite acrale all’esordio.

Unilateral psoriatic arthritis in hemiparesis

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