F. Ortiz-Sanjuán

Tocilizumab in giant cell arteritis: Multicenter open-label study of 22 patients

OBJECTIVE To assess the efficacy of tocilizumab (TCZ) in giant cell arteritis (GCA) patients with refractory disease and/or with unacceptable side effects due to corticosteroids. METHODS A retrospective multicenter open-label study on 22 GCA patients treated with TCZ at standard dose of 8mg/kg/month. The main outcomes were achievement of disease remission and reduction of corticosteroid dose. RESULTS The mean age ± standard deviation of patients was 69 ± 8 years. The main clinical features at TCZ onset were polymyalgia rheumatica (n = 16), asthenia (n = 7), headache (n =5), constitutional symptoms (n = 4), jaw claudication (n = 2), and visual loss (n = 2). Besides corticosteroids and before TCZ onset, 19 of 22 patients had also received several conventional immunosuppressive and/or biologic drugs. Of 22 patients, 19 achieved rapid and maintained clinical improvement following TCZ therapy. Also, after a median follow-up of 9 (interquartile range: 6-19) months, the C-reactive protein level had fallen from 1.9 (1.2-5.4) to 0.2 (0.1-0.9)mg/dL (p < 0.0001) and the erythrocyte sedimentation rate decreased from 44 (20-81) to 12 (2-20)mm/1st hour (p = 0.001). The median dose of prednisone was also tapered from 18.75 (10-45) to 5 (2.5-10)mg/day (p < 0.0001). However, TCZ had to be discontinued in 3 patients due to severe neutropenia, recurrent pneumonia, and cytomegalovirus infection. Moreover, 1 patient died after the second infusion of TCZ due to a stroke in the setting of an infectious endocarditis. CONCLUSION TCZ therapy leads to rapid and maintained improvement in patients with refractory GCA and/or with unacceptable side effects related to corticosteroids. However, the risk of infection should be kept in mind when using this drug in patients with GCA.

Efficacy of Tocilizumab in Conventional Treatment–Refractory Adult-Onset Still's Disease: Multicenter Retrospective Open-Label Study of Thirty-Four Patients†

Adult‐onset Stills disease (AOSD) is frequently refractory to standard therapy. Tocilizumab (TCZ) has demonstrated efficacy in single cases and in small series of patients with AOSD. The aim of this multicenter study was to assess the efficacy of TCZ in patients with AOSD refractory to conventional treatment.

Henoch-Schönlein purpura in northern Spain: clinical spectrum of the disease in 417 patients from a single center.

AbstractThe severity of clinical features and the outcomes in previous series of patients reported with Henoch-Schönlein purpura (HSP) vary greatly, probably due to selection bias. To establish the actual clinical spectrum of HSP in all age groups using an unselected and wide series of patients diagnosed at a single center, we performed a retrospective review of 417 patients classified as having HSP according to the criteria proposed by Michel et al. Of 417 patients, 240 were male and 177 female, with a median age at the time of disease diagnosis of 7.5 years (interquartile range [IQR], 5.3–20.1 yr). Three-quarters of the patients were children or young people aged 20 years or younger (n = 315), and one-quarter were adults (n = 102). The most frequent precipitating events were a previous infection (38%), usually an upper respiratory tract infection, and/or drug intake (18.5%) shortly before the onset of the vasculitis. At disease onset the most common manifestations were skin lesions (55.9%), nephropathy (24%), gastrointestinal involvement (13.7%), joint symptoms (9.1%), and fever (6.2%). Cutaneous involvement occurring in all patients, mainly purpuric skin lesion, was the most common manifestation when the vasculitis was fully established, followed by gastrointestinal (64.5%), joint (63.1%), and renal involvement (41.2%). The main laboratory findings were leukocytosis (36.7%), anemia (8.9%), and increased serum IgA levels (31.7%). The most frequent therapies used were corticosteroids (35%), nonsteroidal antiinflammatory drugs (14%), and cytotoxic agents (5%). After a median follow-up of 12 months (IQR, 2–38 mo), complete recovery was observed in most cases (n = 346; 83.2%), while persistent, usually mild, nephropathy was observed in only 32 (7.7%) cases. Relapses were observed in almost a third of patients (n = 133; 31.9%).In conclusion, although HSP is a typical vasculitis affecting children and young people, it is not uncommon in adults. The prognosis is favorable in most cases, depending largely on renal involvement.

Efficacy of Anakinra in Refractory Adult-Onset Still's Disease: Multicenter Study of 41 Patients and Literature Review.

AbstractAdult-onset Stills disease (AOSD) is often refractory to standard therapy. Anakinra (ANK), an interleukin-1 receptor antagonist, has demonstrated efficacy in single cases and small series of AOSD. We assessed the efficacy of ANK in a series of AOSD patients.Multicenter retrospective open-label study. ANK was used due to lack of efficacy to standard synthetic immunosuppressive drugs and in some cases also to at least 1 biologic agent.Forty-one patients (26 women/15 men) were recruited. They had a mean age of 34.4 ± 14 years and a median [interquartile range (IQR)] AOSD duration of 3.5 [2–6] years before ANK onset. At that time the most common clinical features were joint manifestations 87.8%, fever 78%, and cutaneous rash 58.5%. ANK yielded rapid and maintained clinical and laboratory improvement. After 1 year of therapy, the frequency of joint and cutaneous manifestations had decreased to 41.5% and to 7.3% respectively, fever from 78% to 14.6%, anemia from 56.1% to 9.8%, and lymphadenopathy from 26.8% to 4.9%. A dramatic improvement of laboratory parameters was also achieved. The median [IQR] prednisone dose was also reduced from 20 [11.3–47.5] mg/day at ANK onset to 5 [0–10] at 12 months. After a median [IQR] follow-up of 16 [5–50] months, the most important side effects were cutaneous manifestations (n = 8), mild leukopenia (n = 3), myopathy (n = 1), and infections (n = 5).ANK is associated with rapid and maintained clinical and laboratory improvement, even in nonresponders to other biologic agents. However, joint manifestations are more refractory than the systemic manifestations.

Urticarial vasculitis in northern Spain: clinical study of 21 cases.

AbstractUrticarial vasculitis (UV) is a subset of cutaneous vasculitis (CV), characterized clinically by urticarial skin lesions of more than 24 hours’ duration and histologically by leukocytoclastic vasculitis. We assessed the frequency, clinical features, treatment, and outcome of a series of patients with UV. We conducted a retrospective study of patients with UV included in a large series of unselected patients with CV from a university hospital. Of 766 patients with CV, UV was diagnosed in 21 (2.7%; 9 male and 12 female patients; median age, 35 yr; range, 1–78 yr; interquartile range, 5–54 yr). Eight of the 21 cases were aged younger than 20 years old. Potential precipitating factors were upper respiratory tract infections and drugs (penicillin) (n = 4; in all cases in patients aged <20 yr), human immunodeficiency virus (HIV) infection (n = 1), and malignancy (n = 1). Besides urticarial lesions, other features such as palpable purpura (n = 7), arthralgia and/or arthritis (n = 13), abdominal pain (n = 2), nephropathy (n = 2), and peripheral neuropathy (n = 1) were observed. Hypocomplementemia (low C4) with low C1q was disclosed in 2 patients. Other abnormal laboratory findings were leukocytosis (n = 7), increased erythrocyte sedimentation rate (n = 6), anemia (n = 4), and antinuclear antibody positivity (n = 2). Treatment included corticosteroids (n = 12), antihistaminic drugs (n = 6), chloroquine (n = 4), nonsteroidal antiinflammatory drugs (n = 3), colchicine (n = 2), and azathioprine (n = 1). After a median follow-up of 10 months (interquartile range, 2–38 mo) recurrences were observed in 4 patients. Apart from 1 patient who died because of an underlying malignancy, the outcome was good with full recovery in the remaining patients. In conclusion, our results indicate that UV is rare but not exceptional. In children UV is often preceded by an upper respiratory tract infection. Urticarial lesions and joint manifestations are the most frequent clinical manifestation. Low complement serum levels are observed in a minority of cases. The prognosis is generally good, but depends on the underlying disease.

Single-organ cutaneous small-vessel vasculitis according to the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides: a study of 60 patients from a series of 766 cutaneous vasculitis cases

OBJECTIVE Cutaneous vasculitis (CV) encompasses a wide group of entities characterized by inflammation of skin blood vessels. The term single-organ vasculitis was recently coined by the 2012 Chapel Hill Consensus Conference (CHCC) to define vasculitis affecting a single organ. To our knowledge there are no published reports on single-organ cutaneous small vessel vasculitis (SoCSVV). Our aim was to characterize this entity from a wide series of patients with CV. METHODS We analysed cases of SoCSVV from a series of 766 patients with CV from a single university referral centre. According to 2012 CHCC, the following conditions were required to define SoCSVV: (i) skin biopsy showing characteristic leucocytoclastic vasculitis and (ii) vasculitis limited to skin. RESULTS We included 60 patients (26 women and 34 men) with a mean age of 56 years. The main precipitating factors for SoCSVV were drugs [26 patients (52%)] and previous infection [17 patients (34%)]. The main clinical manifestations were palpable purpura (81.7%) and fever (18.3%). The most frequent laboratory findings were leucocytosis and elevated ESR. Nearly one-quarter of patients with SoCSVV required pharmacological therapy. Corticosteroids (15%) and NSAIDs (13.3%) were the main agents prescribed. After a median follow-up of 4 months, complete recovery was observed in all the patients, although relapses occurred in 8% of patients. CONCLUSION SoCSVV defined according to the 2012 CHCC may be considered a benign disease usually associated with drugs and/or a previous infection.

Drug-associated Cutaneous Vasculitis: Study of 239 Patients from a Single Referral Center

Objective. The 2012 International Chapel Hill Consensus Conference on the Nomenclature of Vasculitides defined drug-associated immune complex vasculitis as a distinct entity included within the category of vasculitis associated with probable etiology. In the present study we assessed the clinical spectrum of patients with drug-associated cutaneous vasculitis (DACV). Methods. Case records were reviewed of patients with DACV treated at a tertiary referral hospital over a 36-year period. A diagnosis of DACV was considered if the drug was taken within a week before the onset of the disease. Results. From a series of 773 unselected cutaneous vasculitis cases, 239 patients (30.9%; 133 men and 106 women; mean age 36 yrs) were diagnosed with DACV. Antibiotics (n = 149; 62.3%), mainly β-lactams and nonsteroidal antiinflammatory drugs (NSAID; n = 24; 10%) were the most common drugs. Besides skin lesions (100%), the most common clinical features were joint (51%) and gastrointestinal (38.1%) manifestations, nephropathy (34.7%), and fever (23.8%). The most remarkable laboratory data were increased erythrocyte sedimentation rate (40.2%), presence of serum cryoglobulins (26%), leukocytosis (24.7%), positive antinuclear antibodies (21.1%), anemia (18.8%), and positive rheumatoid factor (17.5%). Despite drug discontinuation and bed rest, 108 patients (45.2%) required medical treatment, mainly corticosteroids (n = 71) or immunosuppressive drugs (n = 7). After a median followup of 5 months, relapses occurred in 18.4% of patients, and persistent microhematuria or renal insufficiency in 3.3% and 5%, respectively. Conclusion. DACV is generally associated with antibiotics and NSAID. In most cases it has a favorable prognosis, although a small percentage of patients may develop residual renal damage.

Relapses in patients with Henoch-Schönlein purpura: Analysis of 417 patients from a single center

Abstract To further investigate into the relapses of Henoch–Schönlein purpura (HSP), we analyzed the frequency, clinical features, and predictors of relapses in series of 417 unselected patients from a single center. After a median follow-up of 12 (interquartile range [IQR]: 2–38) years, almost one-third of the 417 patients (n = 133; 32%; 85 men/48 women) had experienced at least 1 relapse. At the time of disease diagnosis, patients who later experienced relapses had less commonly infections than those who never suffered flares (30.8% vs 41.9%; P = 0.03). In contrast, patients who experienced relapses had a longer duration of the first episode of palpable purpura than those without relapses (palpable purpura lasting >7 days; 80.0% vs 68.1%; P = 0.04). Abdominal pain (72.3% vs 62.3%; P = 0.03) and joint manifestations (27.8% vs 15.5%; P = 0.005) were also more common in patients who later developed relapses. In contrast, patients who never suffered relapses had a slightly higher frequency of fever at the time of disease diagnosis (9.3% vs 3.8%; P = 0.06). At the time of disease diagnosis, corticosteroids were more frequently given to patients who later had relapses of the disease (44% vs 32% in nonrelapsing patients; P = 0.03). Relapses generally occurred soon after the first episode of vasculitis. The median time from the diagnosis of HSP to the first relapse was 1 (IQR: 1–2) month. The median number of relapses was 1 (IQR 1–3). The main clinical features at the time of the relapse were cutaneous (88.7%), gastrointestinal (27.1%), renal (24.8%), and joint (16.5%) manifestations. After a mean ± standard deviation follow-up of 18.9 ± 9.8 years, complete recovery was observed in 110 (82.7%) of the 133 patients who had relapses. Renal sequelae (persistent renal involvement) was found in 11 (8.3%) of the patients with relapses. The best predictive factors for relapse were joint and gastrointestinal manifestations at HSP diagnosis (odds ratio [OR]: 2.22; 95% confidence interval [CI]: 1.34–3.69, and OR: 1.60; 95% CI: 1.01–2.53, respectively). In contrast, a history of previous infection was a protective factor for relapses (OR: 0.60; 95% CI: 0.38–0.94). In conclusion, joint and gastrointestinal manifestations at the time of diagnosis of HSP are predictors of relapses.

Abatacept in patients with rheumatoid arthritis and interstitial lung disease: A national multicenter study of 63 patients

OBJECTIVE Interstitial lung disease (ILD) is one of the most serious complications of rheumatoid arthritis (RA). In the present study, we aimed to assess the efficacy of abatacept (ABA) in patients with ILD associated to RA. METHODS National multicenter, non-controlled, open-label registry study of RA patients with ILD treated with ABA. RESULTS 63 patients (36 women) with RA-associated ILD undergoing ABA therapy were studied. The mean ± standard deviation age at the time of the study was 63.2 ± 9.8 years. The median duration of RA and ILD from diagnosis were 6.8 and 1 year, respectively. RA was seropositive in 55 patients (87.3%). In 15 (23.8%) of 63 patients the development of ILD was closely related to the administration of synthetic or biologic disease modifying anti-rheumatic drugs. After a follow-up of 9.4 ± 3.2 months, two-thirds of patients remained stable whereas one-quarter experienced improvement in the Modified Medical Research Council scale. At that time forced vital capacity remained stable in almost two-thirds of patents and improved in one out of five patients assessed. Also, diffusing capacity of the lung for carbon monoxide remained stable in almost two-thirds and showed improvement in a quarter of the patients assessed. At 12 months, 50% of the 22 patients in whom chest HRCT scan was performed due persistence of respiratory symptoms showed stabilization, 8 (36.4%) improvement and 3 worsening of the HRCT scan pattern. Eleven of 63 patients had to discontinue ABA, mainly due to adverse events. CONCLUSION ABA appears to be an effective in RA-associated ILD.

SAT0345 Histopathological Differences between Single-Organ Cutaneous Small Vessel Vasculitis and Other Cutaneous Vasculitis Associated with Systemic Involvement

Background Cutaneous vasculitis (CV) encompasses a wide and heterogeneous group of disorders characterized by the presence of necrotizing inflammatory lesions in the cutaneous blood vessels. Single-organ cutaneous small vessel vasculitis (SoCSVV) is, according to 2012 Chapel-Hill criteria, a vasculitis confined to the skin. Objectives Our aim was to compare the histopathological findings of skin biopsies from patients with SoCSVV and those with systemic involvement. Methods From a series of patients with CV, we selected 3 groups: group a) SoCSVV; group b) CV with systemic involvement; group c) subgroup of patients of group b with involvement of 3 organs other than the skin. A comparative study between the group a) with the other two groups (b and c) was performed. Results Group a) was integrated by 9 patients (7 W/2 M; mean age, 64±16 years). In the group b) 43 patients were included (18 W/25M; mean age, 54±21 years). The underlying conditions were: severe bacterial infections (n=12), hypersensitivity vasculitis with involvement of other organs besides the skin (n=10), HSP (n=9), panarteritis nodosa (n=4), microscopic polyangiitis (n=2), cryoglobulinemia (n=2), malignancy (n=2), SLE (n=1) and Sjögrens syndrome (n=1). Finally, 7 patients (3 W/4 M; mean age, 50 ± 20 years) were included in group c). The underlying conditions were: severe bacterial infections (n=3), HSP (n=3) and cryoglobulinemia (n=1). The results of histopathological comparison of group a) with the groups b) and c) are shown in the table. Although no parameter reached statistical significance, in our series we observed that the greater systemic involvement was more frequently associated with tissue neutrophilia, pustular dermatosis and deep involvement of arterioles. By contrast, SoCSVV tend to develop greater tissue eosinophilia and tissue lymphocytosis, whilst the intensity of the inflammatory infiltrate was lower. On the other hand, none of the samples of patients with SoCSVV showed involvement of deep arterioles. SoCSVV (a) CV with systemic involvement (b) CV with involvement of 3 organs besides the skin (c) (n=9) (n=43) (n=7) Hodge index#, mean±SD 6±1 7±3 6±1 Tissue eosinophilia 3 (33.3%) 5 (11.6%) 0 (0%) Tissue neutrophilia 4 (44.4%) 32 (74.4%) 7 (100%) Tissue lymphocytosis 2 (22.2%) 4 (9.3%) 0 (0%) Intensity of inflammatory infiltrate, mean±SD 1±0 1.4±0.7 1.1±0.3 Pustular dermatosis 1 (11.1%) 11 (25.6%) 2 (28.6%) Deep arterioles involvement 0 (0%) 5 (11.6%) 1 (14.3%) #Hodge SJ, et al. J Cutan Pathol. 1987; 14: 279–84. Conclusions In this series we observed that qualitative and quantitative histological differences were correlated with the degree of systemic involvement. However, these results need to be tested in prospective studies with a larger number of patients. Acknowledgement “Fondo de Investigaciones Sanitarias” PI12/00193 (Spain) and RETICS Programs, RD08/0075 (RIER) and RD12/0009/0013 from “Instituto de Salud Carlos III” (ISCIII) (Spain). Disclosure of Interest None declared