Dario Graceffa

Role of the complement system in rheumatoid arthritis and psoriatic arthritis: Relationship with anti-TNF inhibitors

The complement system is an essential component of innate immunity and also plays an important role in modulating adaptive immunity. It comprises more than 30 plasma and membrane-bound proteins and can be activated through three pathways: the classical, the alternative and the lectin pathways. Its activation contributes to the pathogenesis of several autoimmune and inflammatory conditions. The evidence of complement activation in synovial fluid of Rheumatoid Arthritis (RA) patients is abundant, while few data exist in Psoriatic Arthritis (PsA) patients. Levels of complement proteins are generally depressed in the synovial fluid of patients with RA, reflecting consumption of complement. On the other hand, elevated levels of several complement cleavage products have been observed in synovial fluid. Involvement of complement in the pathogenesis of RA was also confirmed in animal models of arthritis: mice deficient for complement proteins are protected against the development of collagen-induced arthritis and administration of the anti-C5 monoclonal antibody prevents the onset of this arthritis. In the last decade anti-tumor necrosis factor agents have shown to be effective for the treatment of both RA and PsA and some studies suggest that the interaction between TNFα and complement system may contribute to the pathogenesis of these diseases. Reduction of the complement activation could be one of the mechanism by which TNFα-inhibitors exert their effectiveness in inflammatory arthritides. Because of these findings, complement could be an attractive therapeutic target both in RA and in PsA.

Anti-TNFα discontinuation in rheumatoid and psoriatic arthritis: Is it possible after disease remission?

Anti-TNFα blockers have rapidly become a standard treatment for rheumatoid (RA) and psoriatic arthritis (PsA) because of their acceptable safety profile and efficacy. Clinical and radiological remission may now be a realistic outcome and constitutes the best achievable state. However, clinical practice guidelines and consensus statements on the criteria of introduction, duration and cessation of treatment are under constant revision. Evidence supports that the early use of biologic DMARDs would produce rapid and sustained suppression of inflammatory disease and preserve function and joint erosions. Proof of this concept, anti-TNFα agents would be effective in maintaining response after cessation of treatment. Conversely, when therapy with anti-TNFα is withdrawn, the disease rapidly returns. Remission may be defined as minimal or no clinically detectable disease activity in the presence of continuing drug treatment and a rapid control of disease activity may prevent irreversible damage and disability. The use of US-PD and MRI in the early detection of disease recurrence could become necessary to prevent the relapse and direct the clinicians choice concerning a re-treatment regimen. The use of biological treatment can be for a limited period, at a time when it has the greatest opportunity to make the difference.

Management of psoriasis patients with hepatitis B or hepatitis C virus infection

The systemic therapies available for the management of Psoriasis (PsO) patients who cannot be treated with more conservative options, such as topical agents and/or phototherapy, with the exception of acitretin, can worsen or reactivate a chronic infection. Therefore, before administering immunosuppressive therapies with either conventional disease-modifying drugs (cDMARDs) or biological ones (bDMARDs) it is mandatory to screen patients for some infections, including hepatitis B virus (HBV) and hepatitis C virus (HCV). In particular, the patients eligible to receive an immunosuppressive drug must be screened for the following markers: antibody to hepatitis B core, antibody to hepatitis B surface antigen (anti-HBsAg), HBsAg, and antibody to HCV (anti-HCV). In case HBV or HCV infection is diagnosed, a close collaboration with a consultant hepatologist is needed before and during an immunosuppressive therapy. Concerning therapy with immunosuppressive drugs in PsO patients with HBV or HCV infection, data exist mainly for cyclosporine a (CyA) or bDMARDs (etanercept, adalimumab, infliximab, ustekinumab). The natural history of HBV and HCV infection differs significantly as well as the effect of immunosuppression on the aforementioned infectious diseases. As a rule, in the case of active HBV infection, systemic immunosuppressive antipsoriatic therapies must be deferred until the infection is controlled with an adequate antiviral treatment. Inactive carriers need to receive antiviral prophylaxis 2-4 wk before starting immunosuppressive therapy, to be continued after 6-12 mo from its suspension. Due to the risk of HBV reactivation, these patients should be monitored monthly for the first 3 mo and then every 3 mo for HBV DNA load together with transaminases levels. Concerning the patients who are occult HBV carriers, the risk of HBV reactivation is very low. Therefore, these patients generally do not need antiviral prophylaxis and the sera HBsAg and transaminases dosing can be monitored every 3 mo. Concerning PsO patients with chronic HCV infection their management with immunosuppressive drugs is less problematic as compared to those infected by HBV. In fact, HCV reactivation is an extremely rare event after administration of drugs such as CyA or tumor necrosis factor-α inhibitors. As a rule, these patients can be monitored measuring HCV RNA load, and ALT, aspartate transaminase, gamma-glutamyl-transferase, bilirubin, alkaline phosphatase, albumin and platelet every 3-6 mo. The present article provides an updated overview based on more recently reported data on monitoring and managing PsO patients who need systemic antipsoriatic treatment and have HBV or HCV infection as comorbidity.

Remission of psoriatic arthritis after etanercept discontinuation: analysis of patients' clinical characteristics leading to disease relapse.

Psoriatic arthritis is a chronic, inflammatory, disabling arthritis affecting up to 30% of psoriatic patients. Recently, it has been demonstrated that tumor necrosis factor alpha (TNF-α) plays a pivotal role in inducing and maintaining joint damage and that molecules that block this cytokine are effective in the treatment of psoriatic arthritis. Etanercept is a recombinant fusion protein acting as a competitive inhibitor of TNF-α, and numerous clinical trials have demonstrated its efficacy in determining psoriatic arthritis remission. However, specific criteria defining psoriatic arthritis remission have not been delineated and few data describing the length of the remission after etanercept discontinuation are available. The aim of this observational, retrospective study was to assess post-remission efficacy maintenance and relapse characteristics after etanercept interruption in patients with moderate-to-severe peripheral psoriatic arthritis (PsA) and cutaneous involvement.

Capillaroscopy in Psoriatic and Rheumatoid Arthritis: A Useful Tool for Differential Diagnosis

Impairment of capillaries permeability and changes of microcirculation are associated with inflammatory arthritis. In order to demonstrate microvascular differences between psoriatic arthritis (PsA) and rheumatoid arthritis (RA) we analyzed capillaroscopic abnormalities such as megacapillaries, haemorrhages, ramifications, and avascular areas in patients affected by these two rheumatic disorders. Moreover to identify specific capillaroscopy patterns we analyzed the following parameters: venous limb diameter, arterial limb diameter, capillary loop diameter, amplitude of the capillary loop, linear density of capillaries (on 2 mm), and number of twisted capillaries (on 4 mm). Through a comparative morphometric analysis of capillaroscopy, our study demonstrated the presence of specific microvascular differences between PsA and RA providing an additional diagnostic tool for the differential diagnosis. We also suggest that capillaries structural abnormalities might reflect endothelial injury due to systemic inflammation during chronic arthritis.

Clinical and contrast-enhanced ultrasound echography outcomes in psoriatic arthritis patients after one year of continuous therapy with anti-TNF drugs

Background. We wanted to verify retrospectively the proportion of patients with psoriatic arthritis who were in remission after 1 year of continuous therapy with either etanercept or adalimumab. Remission was defined as the absence of both clinical and contrast-enhanced ultrasound (CEUS) findings suggestive of joint inflammation. Patients and Methods. The data of twenty-five patients with psoriatic arthritis were available for the clinical and CEUS evaluations before and after 1 year of continuous therapy with etanercept or adalimumab. The count of swollen (ACR66), tender (ACR68), and active inflamed joints (AJC) was used to measure the severity of joint involvement. PASI was used to score the severity of psoriasis. HAQ, DLQI, VAS pain, and VAS itching were administered to each patient before starting therapy and every 3 months, up to 1 year. Results. Eight (32%) out of twenty-five patients were in remission after 1 year of therapy with etanercept or adalimumab. A significant reduction of all clinical variables analysed was seen during the course of therapy. Conclusion. Although a significant proportion of patients achieved remission of arthritis after 1 year of effective anti-TNF therapy, the majority of them continued to have either clinical or CEUS findings suggestive of persistence of joint inflammation.

A case of juvenile pityriasis rubra pilaris type III successfully treated with etanercept

Dear Editor, Pityriasis rubra pilaris (PRP) is a chronic papulo-squamous skin disorder of unknown etiology and considerable clinical heterogeneity. Five types of PRP are clinically recognized according to the Griffiths classification (Griffiths, 1980). Among children, the juvenile classical form (type III) is the most common type. It usually runs a benign course with remission in 1–2 years. However, a chronic, resistant course has been reported in some cases (Sehgal & Srivastava, 2006). Several drugs have been used to treat PRP including retinoids, methotrexate, and more recently biologic drugs (Gemmeke, Sch€ onlebe, Koch, & Wollina, 2010; Ross et al., 2016). At present only 3 cases have been reported of PRP patients less than 18 year old treated with biologics (Cox, Lesesky, Garcia, & O’Grady, 2008; G omez, Ruelas, Welsh, Arcaute, & Ocampo-Candiani, 2007; Kim, Chae, Park, Byun, & Youn, 2015). Here we describe a 13 years old patient affected by type III PRP successfully treated with etanercept.

How effective is ustekinumab in controlling psoriatic arthritis

Recently ustekinumab has been approved for the therapy of psoriatic arthritis (PsA). Some case series have been published reporting new onset of inflammatory arthritis in psoriasis patients treated with ustekinumab. In addition, flare of joint inflammation in PsA patients has also been reported. We describe a case series of seven patients affected by PsA who experienced either a worsening or a flare of inflammatory arthritis during treatment with ustekinumab.

Psoriatic Arthritis during Treatment with Bevacizumab for Anaplastic Oligodendroglioma

Bevacizumab is a recombinant humanised monoclonal antibody directed against the vascular endothelial growth factor (VEGF). The drug, alone or in combination with other anticancer agents, has been shown to be effective against several types of neoplasms. We report a case of a woman with a history of severe psoriasis who developed psoriatic arthritis during a course of bevacizumab, which was administered for a malignant glioma.