Successful Use of Certolizumab Pegol for Refractory Psoriatic Arthritis Triggered by COVID-19 Infection.

Recently, the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has spread worldwide. Although nearly all patients incur mild-to-moderate disease from this viral infection, some develop severe manifestations with a poor prognosis. COVID-19 can also induce autoimmune disease; several cases of arthritis following COVID-19 have been documented in the literature, such as reactive arthritis and chronic arthritis. We herein report a case of psoriatic arthritis triggered by COVID-19. Although the arthritis had been refractory to glucocorticoids and methotrexate, certolizumab pegol subsequently led to remission.

Commensurate incidence and outcomes of liver enzyme elevation between anti-tumor necrosis factor users with or without prior hepatitis B virus infections.

BACKGROUND AND OBJECTIVE: Potential hepatoxicity is an important clinical concern when administering immunosuppressive therapies to patients infected by hepatitis B virus (HBV). Tumor necrosis factor inhibitors (anti-TNF) increase the likelihood of hepatitis consequent to HBV reactivation, but reported risks and outcomes vary. We determined the risks of liver enzyme elevation in anti-rheumatic drug users from an HBV-endemic region with differing HBV serostatus. METHODS: We established retrospective cohorts with rheumatoid arthritis, ankylosing spondylitis, or psoriasis/psoriatic arthritis who: 1) received anti-TNF agents from 1 January 2004 to 30 June 2013; 2) received care from 1 June 2011 to 30 June 2013 but only ever used conventional disease-modifying anti-rheumatic drugs (DMARDs). Serology results defined three subgroups: HBV surface antigen positive (HBsAg+), HBsAg negative/HBV core antibody positive (HBsAg-/HBcAb+), or uninfected. We compared incidences of serum alanine aminotransferase (ALT) exceeding twice the upper reference limit between HBV serostatus subgroups in each treatment cohort. RESULTS: Among 783 patients treated with anti-TNF (n = 472) or DMARDs only (n = 311), HBsAg-/HBcAb+ anti-TNF users had incidence of ALT elevation commensurate with uninfected counterparts (6.1 vs. 6.0/100 person-years), compared to 19.6/100 person-years in HBsAg+ patients (standardized rate ratio 3.3, 95% CI 1.3-8.2); none effected had severe or fatal hepatitis and ALT levels in all HBsAg-/HBcAb+ patients remained stable, mostly normalizing spontaneously, or after moderating treatment. Patterns of of ALT elevation associated with differing HBV serostatus in the DMARD cohort, resembled those in anti-TNF users. CONCLUSIONS: In this large HBV-endemic cohort, the absolute incidence of ALT elevation in anti-TNF users was more than three-fold higher in HBsAg+ patients than in uninfected counterparts; however, no such association was evident in patients with HBsAg-/HBcAb+ serotype, whose risk and outcomes of liver enzyme elevation were similar to uninfected patients, suggesting that anti-TNF use by HBsAg-/HBcAb+ patients is probably safe.

Mercury Exposure in a Riverside Amazon Population, Brazil: A Study of the Ototoxicity of Methylmercury

Introduction Mercury poisoning causes hearing loss in humans and animals. Acute and long-term exposures produce irreversible peripheral and central auditory system damage, and mercury in its various forms of presentation in the environment is ototoxic. Objective We investigated the otoacoustic emissions responses in a riverside population exposed to environmental mercury by analyzing the inhibitory effect of the medial olivocochlear system (MOCS) on transient otoacoustic emissions (TEOAE). Methods The purpose of the research was to evaluate the entire community independently of variables of sex and age. All of the participants were born and lived in a riverside community. After otolaryngologic evaluation, participants were received tympanometry, evaluation of contralateral acoustic reflexes, pure tone audiometry, and recording of TEOAEs with nonlinear click stimulation. Hair samples were collect to measure mercury levels. Results There was no significant correlation between the inhibitory effect of the MOCS, age, and the level of mercury in the hair. Conclusions The pathophysiological effects of chronic exposure may be subtle and nonspecific and can have a long period of latency; therefore, it will be important to monitor the effects of mercury exposure in the central auditory system of the Amazon population over time. Longitudinal studies should be performed to determine whether the inhibitory effect of the MOCS on otoacoustic emissions can be an evaluation method and diagnostic tool in populations exposed to mercury. .

Prevalence of past and reactivated viral infections and efficacy of cyclosporine A as monotherapy or in combination in patients with psoriatic arthritis--synergy study: a longitudinal observational study.

We have prospectively evaluated psoriatic arthritis (PsA) patients for (1) seropositivity for former viral infections and seroconversion and (2) efficacy of cyclosporine A (CsA) alone or in combination with other immunosuppressants in a time period of 12 months. Screening included HBV antibodies and antigens, HCV antibodies and RNA, HSV 1-2, HZV, EBV, and CMV IgG, and IgM, HHV-6 DNA, and HIV 1-2 antibodies. PsA was evaluated by the Psoriasis Area Severity Index (PASI), the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and the Visual Analogue Scale (VAS). At baseline, 126 (56%) out of 225 evaluable patients had 2 or more seropositivities indicative of former infections, and 31 patients (13.8%) presented seropositivity for HCV, HBV, HSV-1 and -2, HHV-6, EBV, or parvovirus infection; one of them, positive for HBAg, was treated with lamivudine, while the remaining 30 received no specific treatment. None of the 31 patients developed virus reactivation. A reduction (P < 0.001) of PASI, BASDAI, and VAS scores was observed at 6 and 12 months. The treatment of PsA with CsA as monotherapy or in combination was safe and effective. In vitro experiments and clinical findings, including those from our study, suggest that CsA as monotherapy or in combination with biologics might be the treatment of choice in PsA HCV-positive patients.

Spondyloarthritis in sub-Saharan Africa.

Spondyloarthritis (SpA) is generally uncommon in sub-Saharan Africa, in part because of the rarity of HLA-B27 in this region. However, the relationship between HLA-B27 and SpA, particularly ankylosing spondylitis (AS), is complex. Despite the HLA-B 27:05 risk allele occurring in some West African populations, associated AS is not seen. In fact, most patients with AS are HLA-B27-negative, although there is emerging evidence that another class I HLA molecule, HLA-B 14:03, is associated with AS in black Africans. The Assessment of SpondyloArthritis International Society criteria for detecting early axial disease are of limited value in sub-Saharan Africa, because of both the rarity of HLA-B27 and very limited access to magnetic resonance imaging. Reactive arthritis (ReA), psoriatic arthritis, and undifferentiated SpA are seen mainly in the context of HIV infection, although the exact effect of the virus in the pathogenesis of arthritis is unclear. In Zambia, ReA is associated with the HLA-B*57:03 allele, which is paradoxically also associated with slow progression of HIV infection. HIV-associated ReA has a more protracted and aggressive course than standard ReA. Enthesitis-related arthritis is more common in children infected with HIV by vertical mother-to child transmission. Use of TNF inhibitors for axial disease is problematic, mainly because of cost, but also because of potential safety problems, especially reactivation of tuberculosis.

The use of anti-tumour necrosis factor therapy in HIV-positive individuals with rheumatic disease.

OBJECTIVE: The purpose of this study was to examine the safety and efficacy of anti-tumour necrosis factor (TNF) agents (etanercept, infliximab and adalimumab) in HIV-positive patients with rheumatic diseases refractory to standard therapy. METHODS: Patients were treated with anti-TNF blocker with rheumatic diseases refractory to disease modifying antirheumatic drugs who had a CD4 count of >200 mm3 and an HIV viral load of <60 000 copies/mm3 and no active concurrent infections. Changes in CD4 counts, HIV viral loads, or other adverse effects while on anti-TNF agents and clinical response were monitored for 28.1 (SD 20.9) months (range 2.5-55). RESULTS: Eight HIV-positive patients were treated with anti-TNF blockers (two patients with rheumatoid arthritis, three with psoriatic arthritis, one with undifferentiated spondyloarthritis, one with reactive arthritis and one with ankylosing spondylitis). No significant clinical adverse effect was attributed to this treatment in any patient. CD4 counts and HIV viral load levels remained stable in all patients. Three patients on etanercept therapy and two patients on infliximab had sustained clinical improvement in their rheumatic diseases. CONCLUSIONS: This retrospective series of eight patients suggests that treatment with anti-TNF-alpha therapy is a viable alternative in HIV patients without advanced disease with associated rheumatic diseases refractory to standard therapy.

Inhibition of TNFalpha does not induce viral reactivation in patients with chronic hepatitis C infection: two cases.

Chronic infections, such as hepatitis C, in the setting of rheumatic disorders pose a potential hindrance to optimal management because of possible complications linked to the institution of immune suppression, as well as the high incidence of hepatotoxicity associated with many of the disease-modifying antirheumatic drugs included in the conventional therapeutic regimens. In the setting of hepatitis C, however, the effect of TNFalpha blockade may be potentially beneficial because TNFalpha appears to be involved in the pathogenesis of liver fibrosis through the stimulation of apoptotic pathways. Data related to this subject are, unfortunately, still limited and without detailed information regarding the clinical progression of the rheumatic disorder. We report the cases of two patients, one with ankylosing spondylitis and one with psoriatic arthritis, who were efficiently treated long-term with anti-TNF agents for their rheumatic disease without any evidence of reactivation or flaring of their hepatitis C infection or deterioration of their liver function. Our results indicate that TNFalpha blockade is a highly efficient and uncompromising therapy in hepatitis C-affected individuals with connective tissue disorders. However, systematic, large-scale studies addressing the issue of safety of these new efficient drugs, i.e., monoclonal antibodies targeted against TNFalpha, in patients with chronic hepatitis C will be needed to properly assess the risks and benefits of this treatment in analogous cases.

Hepatitis C virus infection in psoriatic arthritis.

OBJECTIVE: To evaluate the prevalence of hepatitis C virus (HCV) infection in patients with psoriatic arthritis (PsA), compared with patients affected by non HCV-related rheumatic degenerative disorders. METHODS: One-hundred consecutive subjects with PsA, and a statistically comparable group of 100 consecutive patients with peripheral osteoarthritis (OA) or sciatica due to L4-L5 or L5-S1 herniated disc were tested for HCV infection with a third-generation microparticle enzyme immunoassay (MEIA). Positive cases were submitted to a third-generation recombinant immunoblot assay (RIBA) confirmatory test. Comparison between the HCV prevalence obtained in the 2 enrolled groups was performed using Fisher's exact test. RESULTS: Anti-HCV antibodies were found with the MEIA method, in 1 patient with PsA, and in 4 patients with OA or sciatica. The RIBA method confirmed MEIA results in all positive patients. The difference in HCV prevalence detected in the PsA group and in the control group was not statistically significant (P = 0.68). Furthermore, HCV prevalence in PsA patients was lower than the ones reported in different geographic areas of Italy. CONCLUSION: Our present report does not confirm previous data that indicated an increased prevalence of HCV in PsA patients, and as a consequence, does not sustain a possible trigger role of HCV in cases of PsA. The absence of clinical or instrumental resources that consent a definite differential diagnosis between PsA and HCV-related arthritis was outlined and analyzed.

Replicative multivirus infection with cytomegalovirus, herpes simplex virus 1, and parvovirus B19, and latent Epstein-Barr virus infection in the synovial tissue of a psoriatic arthritis patient.

BACKGROUND: Psoriatic arthropathy occurs as complicating feature in about 5-7% of psoriasis patients. Infectious mechanisms including viral antigens have been suggested by serologic data as CD8 T cellular specifity towards viral epitopes. OBJECTIVE AND RESULTS: We here reported a case of a 32-year-old male psoriatic arthritis patient, where we could demonstrate simultaneous infection with cytomegalovirus (CMV), herpes simplex virus type I (HSV1) and parvovirus B19 (B19), as well as latent Epstein-Barr virus (EBV) infection within the synovial tissue by immunohistochemistry (CMV, parvovirus B19, HSV1, EBV-LMP) and DNA-in situ-hybridization (CMV). Serologic examination revealed positive EBV and parvovirus B19-IgG-antibodies, but no antibody response to HSV1 and CMV. CONCLUSION: This case is of special interest, since replicative viral infections have not yet been demonstrated localised in the psoriatic arthritis synovia. Thus, with particular regard to the limited information of the serologic data and the possible need of immuno suppressive therapy direct synovial testing for viral antigenes may be considered in psoriatic arthritis patients.

Hepatitis C virus and arthritis.

Arthritis is one of the several autoimmune disorders induced by HCV infection. There is not a specific clinical pattern of HCV-related arthritis, but two nonerosive subsets have more frequently been described: a RA-like polyarthritis and a less common mono-oligoarthritis involving medium-sized and large joints, often showing an intermittent course. This latter form is associated with the presence of serum cryoglobulins. Because of its variable characteristics, HCV-related arthritis must be considered in the differential diagnosis of many patients having inflammatory joint involvement. Antikeratin antibodies and possibly IgA RF can be useful in distinguishing between RA and HCV-related RA-like polyarthritis. In fact, these tests are highly specific in RA patients. In any case, the search for HCV antibodies should be more widely performed in the diagnostic approach to rheumatic diseases. An association between PsA and HCV infection has been described in the literature, but the authors were unable to confirm these data. Nonsteroidal anti-inflammatory drugs, hydroxychloroquine, and low doses of corticosteroids are the cornerstones of the treatment of HCV-related arthritis. An etiologic therapy with alpha-interferon and ribavirin is useful when required by hepatic or systemic involvement; such therapy could also be considered in selected cases of isolated arthritis that are unresponsive to other drugs. Few case reports described the onset of polyarthritis after the administration of alpha-interferon for HCV-related chronic hepatitis. This topic should be more accurately studied in the future to exclude a spurious association between the two events.

Etanercept for the treatment of human immunodeficiency virus-associated psoriatic arthritis.

Etanercept may play an important role in modulating the inflammatory activity and progression of human immunodeficiency virus (HIV)-associated psoriasis and psoriatic arthritis. We report the case of a 45-year-old homosexual man with a CD4 cell count of less than 0.05 x 10(9)/L and an HIV viral load of 4200 copies/mL (while receiving highly active antiretroviral therapy) who developed extensive psoriatic plaques, 4.5-kg weight loss, onychodystrophy, and psoriatic arthropathy with severe periarticular bone demineralization. The arthritis progressed despite the use of several disease-modifying medications, including corticosteroids, hydroxychloroquine, and minocycline. Because of uncontrolled, progressive, and disabling arthritis and resulting profound disability, he was treated with etanercept. Within 3 weeks, his psoriasis had improved dramatically and his joint inflammation had stabilized. For the next 4 months, immunologic and viral parameters remained stable, but his clinical course was complicated by frequent polymicrobial infections. Etanercept was thus discontinued despite continued improvements in his psoriasis, psoriatic arthritis, and functional status. While both cutaneous and joint manifestations of psoriasis improved dramatically, the experience with this patient dictates that caution and careful follow-up must be exercised when prescribing etanercept in the setting of HIV infection.

Rheumatic manifestations of HIV-AIDS.

Infection by human immunodeficiency virus is characterized by a myriad of clinical manifestations affecting almost every organ system in the body. If untreated, it follows an inexorable course, leading to a profound state of immunosuppression and eventually death from opportunistic infection and/or development of lymphoproliferative malignancy and Kaposi's sarcoma. Rheumatic manifestations may develop at any time of the clinical spectrum, but usually are more often seen in late stages. A variety of disorders may be seen, particularly Reiter's syndrome and undifferentiated spondyloarthropathy. Most patients do well with conventional anti-inflammatory therapy, but some will require the use of immunosuppressive-cytotoxic therapy.

[Rheumatological manifestations in HIV infections]. / Revmatiske manifestasjoner ved HIV-infeksjon.

BACKGROUND: The recognised clinical spectrum of disease associated with HIV infection is rapidly expanding and now includes a variety of rheumatological manifestations. MATERIAL AND METHODS: In this review of the literature of the last 15 years, we present the most common rheumatic manifestations described in association with HIV infection. RESULTS: Manifestations include a wide array of articular syndromes and autoimmune manifestations such as Reiter's syndrome, psoriatic arthritis, HIV associated arthritis and septic arthritis. Autoimmune diseases associated with HIV infection include a Sjögren-like syndrome, myopathies and systemic vasculitis. INTERPRETATION: Rheumatological manifestations of HIV infection may present earlier than clinical signs of the infection itself. Steroid and cytostatic treatment of rheumatic diseases may worsen the HIV disease.

Psoriatic arthritis and the spectrum of syndromes related to the SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome.

During the past year, the increasing use of nuclear magnetic resonance imaging techniques, with their ability to delineate cartilage and ligamentous structures and to identify edema, are providing a radical improvement in ascertainment of musculoskeletal abnormalities, although their significance remains incompletely delineated. A second theme has come from the study of spondyloarthropathies in different ethnic groups and societal environments, revealing that the Northern European and North American form of the disease, with its powerful association with HLA-B27, is little evident in the rest of the world's population and that different susceptibility genes and environmental factors operate in other regions and peoples. Related to this theme is the compelling evidence of the marked influence of HIV infection on the development of spondyloarthropathies in Africa. Two areas of immune recognition are discussed as examples of emerging fields that may provide useful paradigms for the experimental approach to mechanisms in psoriatic arthritis. One of these is the three-cell model of CD8 T-cell interaction, in which a dendritic cell presents a peptide from an immunogenic protein to both a CD4 and CD8 T-cell clone, providing a cognitive interaction that disrupts tolerance and results in the expansion of the cytotoxic T-cell clone. In this respect, the combination of an activated dendritic cell, together with enhanced availability of arthritogenic microbial antigens caused by microbial persistence, are interesting candidates to explore as the basis of the HIV-associated rheumatic diseases. The second area of immune recognition is the growing understanding of the outline of the solution to the problem of the association of a spondyloarthropathy with several

Hepatitis C virus infection: prevalence in psoriasis and psoriatic arthritis.

OBJECTIVE: To study the prevalence of hepatitis C virus (HCV) infection in 2 groups of patients, one group with psoriasis and the other with psoriatic arthritis (PsA). METHODS: We detected anti-HCV antibodies by ELISA and by a recombinant immunoblot assay (RIBA) in the sera of 50 patients with psoriasis and 50 with PsA. As controls we used a group of 76 patients with rheumatoid arthritis (RA), and referred to data on the prevalence of HCV in the general Italian population. RESULTS: By ELISA, anti-HCV antibodies were detected in 6/50 (12%) patients with PsA, in 5/50 (10%) patients with psoriasis, and in 4/76 (5.2%) patients with RA. All the reactive PsA and RA sera also tested positive on RIBA, while only 3 of the 5 positive results for sera of patients with psoriasis were confirmed by RIBA. The prevalence of HCV infection in patients with psoriasis was not significantly higher than in controls. In contrast, the rate of HCV infection observed in the 50 patients with PsA was higher than that in the other groups, the difference being statistically significant between patients with PsA and the general population. CONCLUSION: Our data do not support the hypothesis that HCV infection may play a role in the pathogenesis of psoriasis. On the other hand they show a statistically significant difference between the prevalence of HCV infection in patients with PsA and the general population.