Therapy of rheumatic polymyalgia: the pathophysiologic management

Polymyalgia rheumatica (PMR) is an inflammatory syndrome affecting older people whose prevalence has increased in recent years. The suppression of the hypothalamic-pituitary-adrenal axis (HPA) and ageing may contribute to the pathogenesis of PMR. Chronic stress (i.e. interpersonal, chronic infections etc.) in elderly people may represent a risk factor for the development of PMR. In fact, elderly represent per se a condition of endocrine senescence including adrenal hypofunction, in addition chronic stress represents a further harmful stimulus to seriously compromise endogenous glucocorticoid production. Synovitis and vasculitis characterize the majority of the patients. Serum cytokine and steroidal hormone patterns suggest that patients with PMR have an intensive inflammatory reaction. As a matter of fact, glucocorticoids represent the most useful temporary "replacement" treatment during the active phase of PMR. The use of modified-release glucocorticoids that might induce higher levels during the night (circadian rhythms as in physiological conditions), will represent another important approach to optimize PMR treatment and reduce the side effects. Combination therapy between glucocorticoids and inhibitors of pro-inflammatory cytokines should be tested in large studies and early cases of PMR

Nailfold capillaroscopy and blood flow laser-doppler analysis of the microvascular damage in systemic sclerosis: preliminary results

Objectives: Systemic sclerosis (SSc) is characterized by altered microvascular structure and function. Nailfold videocapillaroscopy (NVC) is the tool to evaluate capillary morphological structure and laser-Doppler Blood flowmetry (LDF) can be used to estimate cutaneous blood flow of microvessels. The aim of this study was to investigate possible relationships between capillary morphology and blood flow in SSc. Methods: 27 SSc patients and 12 healthy subjects were enrolled. SSc microvascular involvement, as evaluated by NVC, was classified in three different patterns ("Early", "Active", "Late"). LDF analysis was performed at the II, III, IV, V hand fingers in both hands and both at cutaneous temperature and at 36°C. Statistical evaluation was carried out by non-parametric procedures. Results: Blood flow was found significantly lower in SSc patients when compared with healthy subjects (p<0.05). The heating of the probe to 36°C induced a significant increase in peripheral blood flow in all subjects compared to baseline (p <0.05), however, the amount of variation was significantly lower in patients with SSc, compared with healthy controls (p <0.05). The SSc patients with NVC "Late" pattern, showed lower values of peripheral blood flow than patients with NVC "Active" or "Early" patterns (p<0.05). Moreover, a negative correlation between the tissue perfusion score and the progression of the SSc microangiopathy was observed, as well as between the tissue perfusion and the duration of the Raynaud's phenomenon (p <0.03). Conclusions: LDF can be employed to evaluate blood perfusion in the microvascular circulation in SSc patients. The blood flow changes observed with the LDF seem to correlate with the severity of microvascular damage in SSc as detected by NVC

Role of videocapillaroscopy in early detection of transition from primary to secondary Raynaud's fenomenon in systemic sclerosis

Patients initially diagnosed as having primary Raynaud's phenomenon (PRP) may shift to secondary (SRP) during the follow-up. Nailfold videocapillaroscopy (NVC) is a tool that allows to distinguish between PRP and SRP through the identification of the "early" scleroderma-pattern of microangiopathy. The aim of this study was to evaluate the transition from PRP to SRP in an Italian cohort of patients during their follow-up. 129 patients with PRP were identified and followed-up for 2721 months. The diagnosis of PRP was achieved as suggested by LeRoy. The NVC diagnosis of scleroderma-pattern was based on the presence of specific "early" capillary abnormalities (i.e. giant capillaries, microhaemorrhages, and/or slight reduction of capillary density). Based on the identification of the "early" scleroderma-pattern by NVC, 14% of patients changed from PRP to SRP during the follow-up. Interestingly, 4.6% of these patients showed at baseline a fully normal NVC pattern (transition from normal to scleroderma NVC pattern in 3427 months), and 10% showed slight and not-specific nailfold capillary abnormalities (i.e. dystrophic capillaries and/or enlarged capillaries) at baseline (transition to scleroderma NVC pattern in 2515 months). Following a careful NVC analysis, we showed the progression from PRP to SRP in 14% of the analyzed patients. We suggest the capillaroscopic analysis twice a year in presence of PRP, in order to early detect the transition to SRP in patients showing at the beginning a normal pattern or not-specific nailfold capillary abnormalities, as assessed by NVC

Leishmaniasis in rheumatoid arthritis

Leishmaniasis represents a complex of diseases with an important clinical and epidemiological diversity. Visceral leishmaniasis is of higher priority than cutaneous leishmaniasis as it is a fatal disease in the absence of treatment. The clinical spectrum of leishmaniasis and control of the infection are influenced by the parasite-host relationship. The role of cellular immune responses of the Th1 type in the protection against disease in experimental and human leishmaniasis is well established. TNF-α has been implicated in cytokine-induced macrophage activation and tissue granuloma formation, two activities linked to control of intracellular visceral infection caused by Leishmania donovani. Anti- tumor necrosis factor-alpha (TNF-α) strategies have had a marked and substantial impact in the treatment of rheumatoid arthritis, however the clinical use of TNF-α antagonists has been accompanied by increased reporting of infections. Here we report the first case of visceral leishmaniasis in a patient treated for a long period of time with human anti TNF-α monoclonal antibody, adalimumab. Due to the low incidence rate of Mediterranean visceral leishmaniasis, a systematic screening for leishmaniasis in all patients treated with biologics may be not recommended. However, for those patients living at high risk of leishmaniasis exposure, a periodical serological monitoring should be performed during therapy with anti-TNF monoclonal antibodies

Therapy of rheumatic polymyalgia: the pathophysiologic management

Polymyalgia rheumatica (PMR) is an inflammatory syndrome affecting older people whose prevalence has increased in recent years. The suppression of the hypothalamic-pituitary-adrenal axis (HPA) and ageing may contribute to the pathogenesis of PMR. Chronic stress (i.e. interpersonal, chronic infections etc.) in elderly people may represent a risk factor for the development of PMR. In fact, elderly represent per se a condition of endocrine senescence including adrenal hypofunction, in addition chronic stress represents a further harmful stimulus to seriously compromise endogenous glucocorticoid production. Synovitis and vasculitis characterize the majority of the patients. Serum cytokine and steroidal hormone patterns suggest that patients with PMR have an intensive inflammatory reaction. As a matter of fact, glucocorticoids represent the most useful temporary “replacement” treatment during the active phase of PMR. The use of modified-release glucocorticoids that might induce higher levels during the night (circadian rhythms as in physiological conditions), will represent another important approach to optimize PMR treatment and reduce the side effects. Combination therapy between glucocorticoids and inhibitors of pro-inflammatory cytokines should be tested in large studies and early cases of PMR

Endothelin-1 in systemic sclerosis

We evaluated endothelin-1 (ET-1) plasma levels in patients affected by primary Raynaud’s phenomenon (PRP), as well as in patients with systemic sclerosis (SSc) and secondary Raynaud’s phenomenon (SRP). Furthermore, ET-1 levels were investigated in SSc patients with different patterns of peripheral microvascular damage, as evaluated by nailfold videocapillaroscopy (NVC). Methods: 23 PRP patients, 67 SSc patients according to ACR criteria, and 23 healthy subjects were enrolled. SSc microvascular involvement was classified in three different patterns (Early, Active, and Late) by NVC, as previously described. Results: ET-1 was found significantly higher in both PRP and SRP, when compared with controls (median ±IQR: 3.3±2.8, 2.7±2.2, 2.0±2.2, respectively) (p=0.05). No statistically significant difference of ET-1 levels was observed between PRP and SRP patients. ET-1 was found higher in patients with Late NVC pattern, when compared with both Active and Early NVC patterns (median±IQR: 3.4±2.5, 2.4±2.2, 2.5±2.1, respectively), but without statistical significance. Patients with Late NVC pattern showed significantly higher ET-1 plasma levels than controls (p=0.03). No correlation was found between ET-1 levels and disease duration in both groups, as well as between ET-1 levels and age of patients. Conclusions: These data support previous studies, reporting increased ET-1 plasma levels in both PRP and SRP patients. Interestingly, patients with the Late NVC pattern of microangiopathy showed higher ET-1 plasma levels than controls. The high levels of ET-1 detected in the Late NVC pattern of microangiopathy might be related to the larger fibrotic involvement typical of the advanced stages of disease

Role of videocapillaroscopy in early detection of transition from primary to secondary Raynaud’s fenomenon in systemic sclerosis

Patients initially diagnosed as having primary Raynaud’s phenomenon (PRP) may shift to secondary (SRP) during the follow-up. Nailfold videocapillaroscopy (NVC) is a tool that allows to distinguish between PRP and SRP through the identification of the “early” scleroderma-pattern of microangiopathy. The aim of this study was to evaluate the transition from PRP to SRP in an Italian cohort of patients during their follow-up. 129 patients with PRP were identified and followed-up for 2721 months. The diagnosis of PRP was achieved as suggested by LeRoy. The NVC diagnosis of scleroderma-pattern was based on the presence of specific “early” capillary abnormalities (i.e. giant capillaries, microhaemorrhages, and/or slight reduction of capillary density). Based on the identification of the “early” scleroderma-pattern by NVC, 14% of patients changed from PRP to SRP during the follow-up. Interestingly, 4.6% of these patients showed at baseline a fully normal NVC pattern (transition from normal to scleroderma NVC pattern in 3427 months), and 10% showed slight and not-specific nailfold capillary abnormalities (i.e. dystrophic capillaries and/or enlarged capillaries) at baseline (transition to scleroderma NVC pattern in 2515 months). Following a careful NVC analysis, we showed the progression from PRP to SRP in 14% of the analyzed patients. We suggest the capillaroscopic analysis twice a year in presence of PRP, in order to early detect the transition to SRP in patients showing at the beginning a normal pattern or not-specific nailfold capillary abnormalities, as assessed by NVC

Etiopathogenesis of autoimmune hepatitis

Autoimmune hepatitis is a chronic inflammatory liver disease characterized by hypergammaglobulinemia, the presence of autoantibodies, and inflammation within the liver, including lymphocytic infiltrates and interface hepatitis. Autoimmune hepatitis shows a female predominance and can present at any age and in any ethnicity. The disease is thought to be a consequence of a break of immune tolerance leading to an autoimmune process that induces liver injury. The self-attack is triggered by T-helper cell-mediated liver autoantigen recognition and B-cell production of autoantibodies, and is sustained by impaired regulatory T cells number and function. Superimposed on a genetic predisposition, infections and environmental factors have been studied as triggering factors for the disease. Allelic variants in the HLA locus have been associated with susceptibility; associations with single nucleotide polymorphisms within non-HLA genes have also been assessed. Several factors have been described as triggers of autoimmune responses in predisposed individuals, including infections, alcohol, vitamin D deficiency, and an altered composition of the intestinal microbiome. Importantly, drugs and herbal agents may trigger classical autoimmune hepatitis, or may induce a liver disease with autoimmune features. Interactions between female hormones and genetic factors have been hypothesized to play a role in autoimmunity, although the exact role for these factors has not been fully established. Herein we present a review of the etiology of autoimmune hepatitis including de novo autoimmune hepatitis post-liver transplantation as well as animal models for its study. © 201