Search

Background: The rate of viral reactivation in occult HBV carriers (HBsAg-/HBcAb+) in the course of immunosuppressive therapy ranges from 5% to 10%.(1) Nevertheless, anti-TNFalpha therapy was reported to be quite a safe option in HBV occult carriers (i.e. HBsAg-; HBcAb+) patients in Italy(2). Recent data from Taiwan (Cina) pointed out the occurrence of viral reactivation in 1/12 HBV occult carriers patients with Rheumatoid Arthritis (RA) undergoing such treatment(3). Objectives: This abstract is devoted to furtherly address this topic. Methods: Three hundred and three patients(164F, aged 52,4±12,8) with RA or Spondylarthritis (SA) observed from May 2002 to July 2011, were administered anti-TNFalfa treatment for 42±30,5 months. Serological screening for HBV infection with hepatitis B surface antigen (HBsAg), antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface antibody (anti-HBs) was performed in all patients. Moreover, Aminotransferases (ALT, AST) were evaluated at baseline and every 4 weeks. Finally, HBV-DNA evaluation was planned in HBcAb+ HBsAb+/- patients if transaminases would have increased >2 upper normal value in two consecutive determinations. Results: Fifty out of the 303 patients investigated, (25F, aged 58,1±11,2) (16,5%) were HBsAg-/HBcAb +. Out of them 37 were HBsAb + (74%);10 HBsAb- (20%);in 3 patients HBsAb was not available. Ten patients were treated with IFX, 19 with ETA, 17 with ADA and 4 with GOL for 44,5±28,3 months. Twelve patients were also treated with Methotrexate (MTX), 4 with Leflunomide (LFN) and 11 with Prednisone (PDN) (

Background: HBV occult carriers (i.e HBsAg-/HBcAb+) are at risk for viral reactivation under immunosuppressive treatment for cancer and transplantation. Even if rarely, HBV reactivation has been also reported in occult HBV infection patients with Rheumatoid Arthritis (RA) or Spondyloarthritis (SA) undergoing anti TNFα treatment. No data are available on the influence of such treatment on liver architecture. Objectives: This study was devoted to address this topic. Methods: Liver fibrosis, as evaluated by Transient Elastografy (TE), was investigated in 73 patients with RA or SA undergoing anti TNFα treatment. Out of them, 6 were HBcAb+/HBsAb-; 33 HBcAb +/HBsAb+; in 2 HBcAb+, HBsAb was not available; 32 were HBcAb-. The patients were observed for a mean period of 43,9±26,3 months, during which ALT was measured every 4 weeks. HBV-DNA was evaluated if ALT increased more than 2 x upper normal value in 2 consecutive determinations. For each patient, 10 measurement of liver stiffness were performed and reported as average kPa value. A cut off value of 7,3 was assumed to denote significant fibrosis. BMI was calculated in all patients. Results: Out of the seventy three patients (37F, aged 56,9±11,3) investigated, 18 were treated with Infliximab (IFX), 24 with Etanercept (ETA), 24 with Adalimumab (ADA) and 7 with Golimumab (GOL); 20 patients were also treated with Methotrexate (MTX), 10 with Leflunomide (LFN), 26 with Sulfasalazine (SSZ) and 12 with Prednisone (PDN) (0.05). No case of HBV reactivation was recorded. A stiffness value >7,3 KPa was detected in 10/41 (24,4%) anti HBc + patients vs 1/32 (3%) patients anti HBc - (p=0.02). Conclusions: In our series the presence of anti-HBc antibodies identifies a subgroup of patients with liver damage, despite normal ALT values. This suggests that anti-TNFα therapy might promote liver fibrosis in occult HBV carriers or that some anti-HBc positive patients had a past-history of liver damage due to previous active HBV infection. These results await to be assessed in a longitudinal study. References: Calabrese LH, Zein NN, Vassilopoulos. Hepatitis B virus (HBV) with immunosuppressive therapy in rheumatic diseases: assessment and preventive strategies. Ann Rheum Dis 2006;65;983-989. Caporali R et al. Safety of tumor necrosis factor α blockers in hepatitis B virus occult carriers (hepatitis B surface antigen negative/anti-hepatitis B core antigen positive) with rheumatic diseases. Arthritis Care Res. 2010, 749-754. Castera L, Forns X, Alberti A. Non-invasive evaluation of liver fibrosis using transient elastography. J Hepatol. 2008 May;48(5):835-47. Bonino F, Arena U, Brunetto MR, Coco B, Fraquelli M, Oliveri F, Pinzani M, Prati D, Rigamonti C, Vizzuti F; Liver Stiffness Study Group "Elastica" of the Italian Association for the Study of the Liver. Liver stiffness, a non-invasive marker of liver disease: a core study group report. Antivir Ther. 2010;15 Suppl 3:69-78. Disclosure of Interest: None Declared

L’artrite psoriasica (AP) è una malattia infiammatoria, cronica associata alla psoriasi e che viene classificata nelle Spondiloentesoartriti sieronegative (SpA). Si caratterizza per la eterogeneità della presentazione, delle articolazioni colpite e del decorso clinico. In un elevato numero di pazienti, il coinvolgimento poliarticolare è simile a quello dell’artrite reumatoide e pertanto conduce a disabilità ed è responsabile di un’alterata qualità della vita (1). Diventa necessario là dove il quadro clinico artritico e/o l’evoluzione del danno articolare non siano controllabili, il trattamento con i farmaci biologici anti-TNF-alfa (2). Le “interstiziopatie polmonari diffuse” comprendono un gruppo eterogeneo di malattie caratterizzate da alterazioni infiammatorie su base immunitaria interessanti estensivamente l’interstizio alveolare con possibile coinvolgimento delle strutture bronchiali periferiche. Tali patologie hanno in comune l’alveolite e la fibrosi ma non un’unica eziologia, che nella maggior parte dei casi è sconosciuta (3). Descriviamo il caso clinico di un paziente affetto da AP che, in corso di trattamento con infliximab, ha sviluppato un quadro di ILD. Notevoli problematiche sono state affrontate per il trattamento della patologia articolare che si è dimostrata essere controllata dall’etanercept con contemporaneo controllo della patologia respiratoria.

Sir, A 62-year-old Caucasian man was referred to us with multiple erythematous arciform lesions with a wood-grain-like appearance of fifteen months' evolution. The dermatosis had initially affected the patient's legs, extending to his abdomen and arms. His medical history included rheumatoid arthritis, treated with systemic corticosteroids; DMARDs (methotrexate) with folic acid supplements; omeprazole; and cardioaspirin. Interestingly, the resolution of rheumatoid arthritis with various DMARDs was related to the resolution of the dermatosis. Physical examination disclosed an eruption on the legs characterized by irregular, multiple, gyrate bands of erythema bordered on one side by scale and on the other by normal-looking skin. The lesions migrated, leaving a thin scale at the edges and creating a bizarre pattern [Figure 1]. The dermatosis exhibited characteristic rapid movement over hours. Pruritus was moderate. The patient had previously taken oral corticosteroids which had been partially successful, but his condition had worsened rapidly when treatment was interrupted. Histopathological findings were non-specific, showing evidence of hyperkeratosis, orthokeratosis, and a superficial, perivascular, mononuclear infiltrate, which although non-diagnostic, were consistent with changes described for erythema gyratum repens (EGR) [Figure 2]. Several case reports have shown positive direct immunofluorescence (DIF) in the skin: DIF tests on the skin describe deposits of IgG and C3 along the basement membrane zone. [1] However, DIF of involved non-sun-exposed and uninvolved skin was negative in our patient. Figure 1: Clinical presentation on admission Click here to view Figure 2: Histological features of erythema gyratum repens (EGR) included hyperkeratosis, orthokeratosis, and a perivascular inflammatory infiltrate (H and E, ×200) Click here to view Clinical findings were consistent with EGR. The patient had a family history of esophageal cancer, so the search for an associated neoplasm began. Laboratory tumor markers were all normal. Thirty-two months after the onset of EGR, investigations (chest X-ray, gastroscopy, colonoscopy, abdominal ultrasound, computerized tomography of the chest, abdomen and pelvis, and whole body PET-CT) still proved normal. The presentation of the skin disorder was so distinctive that a differential diagnosis was difficult to generate. In our patient, the differential diagnoses included erythema annulare centrifugum (EAC), urticarial vasculitis, and systemic lupus erythematosus. Distinction between EGR and EAC is very difficult, since clinical findings are similar; the histopathologic pictures of both diseases are nonspecific and both can be associated with malignancy (EGR more often). However, one of the differences between them is in the rapidity of movement. EGR exhibits characteristic rapid movement over minutes and hours; EAC moves slowly over days and months. The gyrate erythema presented in this case had clinical features similar to both EGR and EAC, but the rapidity of movement was more consistent with EGR. The differential diagnosis between EGR and urticarial vasculitis was made histopathologically. Urticarial vasculitis typically shows leukocytoclastic vasculitis. Classic symptoms of urticarial vasculitis, such as painful burning sensation, residual purpura, and pigmentation, were not present. Scaling trailing the leading edge of the eruption, which is one of the typical findings of EGR, was present in our case. The patient was studied for tuberculosis; chest X-ray, CT, Mantoux test, and Quantiferon test were all negative. EGR is a rare specific dermatosis, believed to be an obligate paraneoplastic cutaneous syndrome. In more than 80% of cases, EGR is associated with an underlying malignancy and in 80% of cases, this distinctive migratory eruption appears prior to a malignancy diagnosis. EGR can precede 1 to 72 months before malignancy, though the average is 4 to 9 months. Approximately, one-third of patients will manifest lung cancer, 8% esophageal cancer, and 6% an unknown primary. Tumors of the breast, bladder, prostate, cervix, and uterus have also been reported. [2] Here, however, we report a case of EGR which is non-paraneoplastic. Case reports demonstrating an association with non-neoplastic diseases have also been reported, such as pulmonary tuberculosis, drug use, hypereosinophilic syndrome, ichthyosis, autoimmune conditions such as CREST syndrome [3] or disorders with an EGR-like presentation such as tinea imbricata, lupus erythematosus, bullous diseases, resolving pityriasis rubra pilaris, [4] psoriasis, and Sjφgren syndrome. [5] This association may either be an example of an extremely unusual clinical presentation of the primary dermatosis in question, or may be a case of "true" EGR as observed during the course of other non-neoplastic conditions. Healthy patients with this distinctive eruption have been reported in literature, which might cast doubt on the reliability of the diagnosis. To our knowledge, no case of EGR associated with rheumatoid arthritis has, to date, been described in literature, making our case the first reported description of its kind. Moreover, a parallel evolution of the two affections (EGR and rheumatoid arthritis) was observed in our patient. In conclusion, our experience shows that EGR does not necessarily indicate underlying malignancy, but it can be associated with a non-neoplastic disease such as rheumatoid arthritis. References 1. Caux F, Lebbe C, Thomine E, Benyahia B, Flageul B, Joly P, et al. Erythema gyratum repens: A case studied with immunofluorescence, immunoelectronmicroscopy and immunohistochemistry. Br J Dermatol 1994;131:102-7. 2. Hauschild A, Swensson O, Christophers E. Paraneoplastic bullous pemphigoid resembling erythema gyratum repens. Br J Dermatol 1999;140:550-2. 3. Demonchy E, Lacour JP, Ortonne JP, Passeron T. Erythema gyratum repens, not always a bad omen for patients. J Eur Acad Dermatol Venereol 2010;24:738-9. 4. Almaani N, Robson A, Sarkany R, Griffiths WA. Erythema gyratum repens associated with pityriasis rubra pilaris. Clin Exp Dermatol 2011;36:161-4. 5. Matsumura T, Kumakiri M, Sato-Matsumura KC, Ohkawara A. Erythema gyratum repens-like eruption in a patient with Sjögren syndrome. Acta Derm Venereol 1995;75:327.

Scopo del lavoro Valutare l’incidenza di infezioni severe che hanno richiesto ospedalizzazione, di infezioni lievi, di neoplasie e di manifestazioni cutanee (ADR) in pazienti affetti da Artrite Reumatoide sia al primo trattamento con anti-tumor necrosis factor alfa (antiTNFalfa) che dopo switch ad altro antiTNFa Pazienti e metodi Sono stati osservati 160 pazienti (129 F e 31 M con età media 53,6) tutti affetti da AR in terapia con antiTNFalfa valutati con visite a cadenza trimestrale da Ottobre 2002 a Maggio 2011 (92 mesi). Prima dell’inizio del trattamento con antiTNF-alfa, tutti i pazienti erano stati sottoposti a controlli di screening per la TBC e a Rx del torace. Dei 160 pazienti, 52 (32,5%) pazienti avevano presentato ADR e di questi 44 (27,5%) erano stati sottoposti a switch verso un altro antiTNFalfa; 8 pazienti interrompevano la terapia per il tipo di ADR(5%). Tutti i pazienti ricevevano in associazione un DMARD, 99 pazienti avevano ricevuto almeno un trattamento con Etanercept, 99 almeno un trattamento con Adalimumab e 33 pazienti almeno un trattamento con Infliximab. Risultati: Da Ottobre 2002 a Maggio 2011 (92 mesi) su 160 pazienti sono state rilevate 64 ADR agli antiTNFalfa: 52su 160 pazienti avevano manifestato ADR in seguito ad un primo antiTnfalfa; 12su 44 pazienti avevano presentato ADR dopo il secondo antiTNFalfa e 4 pazienti avevano presentato la stessa ADR al 1°e al 2° anti TNF-alfa . Con il primo antiTNFalfa le manifestazioni cutanee erano 5 con Etanercept, 4 con Adalimumab e 0 con Infliximab; le neoplasie 1 con Etanercept ed 1 con Adalimumab; le infezioni ospedalizzate 4 (2 con Infliximab, 1con Etanercept e1 con Adalimumab); le infezioni non ospedalizzate 2 (1con Etanercept e1con Adalimumab).27 pazienti presentavano altro tipo di ADR. Con il secondo antiTNFalfa le manifestazioni cutanee erano 1 con Etanercept, 2 Adalimumab e 0 con Infliximab; le neoplasie erano 0; le infezioni ospedalizzate erano 2 (1 con Etanercept e 1con Adalimumab); le infezioni non ospedalizzate erano 2 (1con Etanercept e 1 con Adalimumab); 5 pazienti presentavano altro tipo di ADR. Conclusioni Questo studio evidenzia un buon profilo di sicurezza dei tre farmaci antiTNFalfa. Non vi è differenza significativa per ADR(p0,6) e per ADR gravi (p0,8)tra primo e secondo antiTNFalfa , Bibliografia: 1) Lee HH, et al. Cutaneous side effects in patients with rheumatic diseases during application of tumour necrosis factor-alpha antagonists. Br J Dermatol 2007 Mar; 156 (3): 486-91. 2) Keystone EC. Does anti-tumor necrosis factor-alpha therapy affect risk of serious infection and cancer in patients with rheumatoid artrhritis?: a review of longoterm data. Journal Rheumatol ogy 2011 May 15.

Background and aim: Ulcerative Colitis (UC) and Crohn’s disease (CD) are the most common forms of Inflammatory Bowel Diseases (IBD) while Aspecific Chronic Colitis (ACC) and Indeterminate Colitis (IC) are less frequent. IBD are frequently complicated by joint involvement (peripheral and axial arthritis). Antibodies recognizing cyclic citrullinated peptides (anti-CCP) are directed to proteins that contain the unusual amino acid citrulline. The anti-CCP ELISA test has an excellent specificity for the diagnosis of Rheumatoid Arthritis (RA), especially in patients with early disease, and it is considered a disease activity predictor. Anti-CCP positivity is detected also in Psoriatic Arthritis (PA) but associated with symmetrical polyarthritis pattern. Correlation between IBD, with or without arthritic manifestations, and anti-CCP positivity was not founded. The aim of our study was to evaluate the role of anti-CCP in IBD patients with arthritic manifestations (Enteropathic Arthritis, EA), with arthritic manifestations and Psoriasis (EA + Ps) and in IBD patients without extraintestinal manifestations. Material and methods: A total of 54 consecutive adult patients with IBD (24: 19 UC, 3 CD and 2 ACC), with EA (16:10 UC, 5 CD and 1 IC) and with EA + Ps (14:6 UC, 7 CD and 1 ACC) were evaluated. Anti-CCP antibodies were detected on patients serum samples by a second generation ELISA test (VCP-IgG Kit; ASTRA Srl Milano) and as positive results were defined values > 25 U/mL. Results: Anti-CCP positivity was detected in 8 of 54 patients (15%): 4 IBD (3 UC and 1 ACC), 2 EA (2 UC) and 2 EA + Ps (1 UC and 1 ACC). No significant difference (p>0.05) of the prevalence of anti-CCP was found among patients with EA, patients with EA + PS and IBD patients without arthritic manifestations and also among the three groups with different articular involvement. Instead, UC patients had significantly higher prevalence (p

In clinical practice, the coincidence of nephrotic syndrome with pheochromocytoma is very rare. The case is described of a 23-year-old woman who in June 1988 presented with recurrent hypertensive crises, severe asthenia, abundant sweats, orthostatic hypertension and massive proteinuria. Diagnostic tests performed (abdominal ultrasound and CT, urinalysis, renal function tests, plasma levels of metanephrine and normetanephrine, as well as urinary VMA determination) revealed the presence of a pheochromocytoma of the left adrenal gland combined with nephrotic syndrome. Surgical removal of the left adrenal led to immediate normalization of blood pressure and absence of urinary abnormalities. The authors therefore suggest either an immunological pathogenesis or one due to glomerular hyperfiltration.