Carmen González-Vela

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.

Anti-TNF-α therapy in refractory uveitis associated with sarcoidosis: Multicenter study of 17 patients

OBJECTIVES To assess anti-TNF-α therapy response in uveitis associated with sarcoidosis refractory to conventional immunosuppressive therapy. METHODS Open-label, multicenter, retrospective study on patients with sarcoid uveitis who underwent anti-TNF-α therapy because of inadequate response to conventional therapy including corticosteroids and at least 1 systemic synthetic immunosuppressive drug. The main outcome measurements were degree of anterior and posterior chamber inflammation, visual acuity, macular thickness, and immunosuppression load. RESULTS A total of 17 patients (8 men; 29 affected eyes; mean ± standard deviation age 38.4 ± 16.8; range: 13-76 years) were studied. The patients had bilateral hilar lymphadenopathy (58.8%), lung parenchyma involvement (47.1%), peripheral lymph nodes (41.2%), and involvement of other organs (52.9%). Angiotensin-converting enzyme was elevated in 58.8%. The most frequent ocular pattern was bilateral chronic relapsing panuveitis. The first biologic agent used was adalimumab in 10 (58.8%) and infliximab in 7 (41.2%) cases. Infliximab 5mg/kg intravenously every 4-8 weeks and adalimumab 40mg subcutaneously every 2 weeks were the most common administration patterns. In most cases anti-TNF-α therapy was given in combination with immunosuppressive drugs. The mean duration of follow-up was 33.9 ± 17.1 months. Significant improvement was observed following anti-TNF-α therapy. Baseline results versus results at 2 years from the onset of biologic therapy were the following: the median of cells in the ocular anterior chamber (interquartile range-IQR) 0.5 (0-2) versus 0 (0-0) (p = 0.003), vitritis 0 (0-1.25) versus 0 (0-0) (p = 0.008), macular thickness (391.1 ± 58.8 versus 247 ± 40.5µm) (p = 0.028), and visual acuity 0.60 ± 0.33 versus 0.74 ± 0.27; p = 0.009. The median daily (interquartile range) dose of prednisone was also reduced from 10 (0-30)mg at the onset of the anti-TNF-α therapy to 0 (0-0)mg at 2 years (p = 0.02). Significant reduction was also achieved in the immunosuppressive load. CONCLUSION Anti-TNF-α therapy is effective in sarcoid uveitis patients refractory to conventional immunosuppressive therapy. Infliximab and adalimumab allowed a substantial reduction in prednisone dose despite having failed standard therapy.

Paradoxical and persistent renal impairment in Henoch-Schonlein purpura after high-dose immunoglobulin therapy.

Dr. Miguel A. González-Gay, MD, PhD, Division of Rheumatology, Hospital Xeral-Calde, c/Dr. Ochoa s/n, E-27004 Lugo (Spain) Dear Sir, Intravenous high-dose immunoglobulin (IVHDI) has proved to be effective in the treatment of several immune-mediated diseases, including systemic vasculitis [1, 2]. In this sense, Rostoker et al. [3, 4] have reported that both lowand high-dose immunoglobulin therapy may be effective in treating either moderate or severe nephritis in Henoch-Schönlein purpura (HSP) and IgA nephropathy (IGAN). However, concern about renal deterioration has been raised in cases of systemic vasculitis and systemic lupus erythematosus following IVHDI [5-7]. We report a patient diagnosed as having HSP who paradoxically presented an acute and persistent renal impairment after IVHDI. A 24-year-old man presented to our hospital with a history of abdominal pain and purpura involving the lower extremities and trunk. He was asymptomatic until 10 days before admission, when he abruptly developed palpable rapidly increasing purpura and edema in his lower extremities. At the emergency room he had colicky abdominal pain and arthralgias in his ankles and knees. The rest of the patient’s history was unremarkable. On examination his temperature was 36 °C, blood pressure 140/80 mm Hg and pulse 80/min. Cardiopulmonary examination was normal. The abdomen was soft with tenderness. Edema and palpable purpura were present in the lower third of the inferior extremities. There were also scattered purpuric lesions in the buttocks. On admission full blood count, coagulation tests, blood chemistry profile and urinalysis were normal. The Westergren erythrocyte sedimentation rate was 22 mm/h. Test for hepatitis B and C, human immunodeficiency virus serology, antinuclear antibodies, cryo-globulins, immunoglobulins (including IgA, IgG and IgM), rheumatoid factor, serum C3 and C4, and ANCA were negative or normal. Chest and abdomen X-ray films, electrocardiogram and echocardiogram were also normal. A skin biopsy showed a leukocytoclastic vasculitis with IgA immune deposits affecting capillaries and venules. Thirty-six hours after admission, nausea, vomiting and an increase in diffuse abdominal pain as well as melena along with new skin lesions were observed. Endoscopic examination showed petechial mucosal lesions in the duodenum. Treatment with 40 mg of intravenous meth-ylprednisolone every 6 h was started. A rapid improvement of the abdominal pain was observed within the first 5 days after the onset of

Primary Acute Torsion of the Vermiform Appendix

A case of primary acute appendiceal torsion in a 6-year-old boy with symptoms suggestive of acute appendicitis is presented. The appendix was abnormally long, measuring 13.5 cm in length. Although appendicitis is the most common intra-abdominal surgical emergency, there are few descriptions of primary acute appendiceal torsion, a rare cause of an acute abdomen. A review of the English language literature disclosed 19 reports, including the present, with 11 pediatric cases. The site of torsion occurs most frequently 1 cm or more from the appendiceal base. Rotation varies from 270 degrees to 1080 degrees with a mean of 580 degrees. The direction of the rotation is more frequently anticlockwise. Appendix is most commonly described as lying free or pelvic. In children the mean age is 9.1 years, the range 3-16 years, and the male-to-female ratio 4.5:1.

Successful effect of tocilizumab in anti-TNF-α-induced palmoplantar pustulosis in rheumatoid arthritis

Anti-tumour necrosis factor-alpha (TNF-α) agents are effective drugs used in several chronic inflammatory diseases such as rheumatoid arthritis (RA). Psoriasiform lesions, including palmoplantar pustulosis, have been described following anti-TNF-α therapy. These lesions often resolve with topical therapy with or without discontinuation of these drugs. However, in some cases, psoriasiform lesions may persist despite anti-TNF-α withdrawal. We report on two RA patients treated with adalimumab (ADA) who developed palmoplantar pustular despite dermatological treatment and ADA discontinuation. Tocilizumab (TCZ) therapy was initiated because of persistence of skin lesions and flare of the disease. Following treatment with this drug, complete resolution of the dermatological lesions and induction of remission of RA was achieved. To the best of our knowledge, management of palmoplantar pustulosis due to TNF-α agents with TCZ leading to both improvement of the disease and resolution of the cutaneous lesions has not previously been reported.

Association of Trabecular Bone Score with Inflammation and Adiposity in Patients with Psoriasis: Effect of Adalimumab Therapy

Studies on trabecular bone score (TBS) in psoriasis are lacking. We aim to assess the association between TBS and inflammation, metabolic syndrome features, and serum adipokines in 29 nondiabetic patients with psoriasis without arthritis, before and after 6-month adalimumab therapy. For that purpose, adjusted partial correlations and stepwise multivariable linear regression analysis were performed. No correlation was found between TBS and disease severity. TBS was negatively associated with weight, BMI, waist perimeter, fat percentage, and systolic and diastolic blood pressure before and after adalimumab. After 6 months of therapy, a negative correlation between TBS and insulin resistance (p = 0.02) and leptin (p = 0.01) and a positive correlation with adiponectin were found (p = 0.01). The best set of predictors for TBS values at baseline were female sex (p = 0.015), age (p = 0.05), and BMI (p = 0.001). The best set of predictors for TBS following 6 months of biologic therapy were age (p = 0.001), BMI (p < 0.0001), and serum adiponectin levels (p = 0.027). In conclusion, in nondiabetic patients with moderate-to-severe psoriasis, TBS correlates with metabolic syndrome features and inflammation. This association is still present after 6 months of adalimumab therapy. Moreover, serum adiponectin levels seem to be an independent variable related to TBS values, after adalimumab therapy.

Isolated Fibrinoid Arteritis of the Prostate

Four cases of apparently asymptomatic isolated fibrinoid arteritis in the prostate are described. All four cases occurred in elderly men with nodular hyperplasia. In all of these cases isolated fibrinoid arteritis was an incidental finding unrelated to the presenting symptoms. The histopathological appearance of the vasculitis was not sufficiently specific to exclude the possibility of systemic polyarteritis nodosa. However, there were no signs of generalized disease. Follow-up studies showed no evidence of disseminated vasculitis. Immunophenotyping of the vascular cellular infiltrate revealed abundant T lymphocytes, significant numbers of histiocytes, and virtual absence of B lymphocytes. The diagnosis of isolated arteritis depends on the exclusion of systemic disease, its excellent prognosis differing dramatically from the more common form of systemic polyarteritis nodosa. Information that isolated arteritis may occur in the prostate is of importance both to avoid misdiagnosis and to prevent unnecessary treatment. Int J Surg Patltol 4(3):00-00, 1997

Predictors of positive 18 F-FDG PET/CT-scan for large vessel vasculitis in patients with persistent polymyalgia rheumatica

OBJECTIVE Polymyalgia rheumatica (PMR) is often the presenting manifestation of giant cell arteritis (GCA). Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scan often discloses the presence of large vessel vasculitis (LVV) in PMR patients. We aimed to identify predictive factors of a positive PET/CT scan for LVV in patients classified as having isolated PMR according to well-established criteria. METHODS A set of consecutive patients with PMR from a single hospital were assessed. All of them underwent PET/CT scan between January 2010 and February 2018 based on clinical considerations. Patients with PMR associated to other diseases, including those with cranial features of GCA, were excluded. The remaining patients were categorized in classic PMR (if fulfilled the 2012 EULAR/ACR classification criteria at disease diagnosis; n = 84) or atypical PMR (who did not fulfill these criteria; n = 16). Only information on patients with classic PMR was assessed. RESULTS The mean age of the 84 patients (51 women) with classic PMR was 71.4 ± 9.2 years. A PET/CT scan was positive in 51 (60.7%). Persistence of classic PMR symptoms was the most common reason to perform a PET/CT scan. Nevertheless, patients with positive PET/CT scan often had unusual symptoms. The best set of predictors of a positive PET/CT scan were bilateral diffuse lower limb pain (OR = 8.8, 95% CI: 1.7-46.3; p = 0.01), pelvic girdle pain (OR = 4.9, 95% CI: 1.50-16.53; p = 0.01) and inflammatory low back pain (OR = 4.7, 95% CI: 1.03-21.5; p = 0.04). CONCLUSION Inflammatory low back pain, pelvic girdle and diffuse lower limb pain are predictors of positive PET/CT scan for LVV in PMR.

Successful Optimization of Adalimumab Therapy in Refractory Uveitis Due to Behçet's Disease

PURPOSE To assess efficacy, safety, and cost-effectiveness of adalimumab (ADA) therapy optimization in a large series of patients with uveitis due to Behçet disease (BD) who achieved remission after the use of this biologic agent. DESIGN Open-label multicenter study of ADA-treated patients with BD uveitis refractory to conventional immunosuppressants. SUBJECTS Sixty-five of 74 patients with uveitis due to BD, who achieved remission after a median ADA duration of 6 (range, 3-12) months. ADA was optimized in 23 (35.4%) of them. This biologic agent was maintained at a dose of 40 mg/subcutaneously/2 weeks in the remaining 42 patients. METHODS After remission, based on a shared decision between the patient and the treating physician, ADA was optimized. When agreement between patient and physician was reached, optimization was performed by prolonging the ADA dosing interval progressively. Comparison between optimized and nonoptimized patients was performed. MAIN OUTCOME MEASURES Efficacy, safety, and cost-effectiveness in optimized and nonoptimized groups. To determine efficacy, intraocular inflammation (anterior chamber cells, vitritis, and retinal vasculitis), macular thickness, visual acuity, and the sparing effect of glucocorticoids were assessed. RESULTS No demographic or ocular differences were found at the time of ADA onset between the optimized and the nonoptimized groups. Most ocular outcomes were similar after a mean ± standard deviation follow-up of 34.7±13.3 and 26±21.3 months in the optimized and nonoptimized groups, respectively. However, relevant adverse effects were only seen in the nonoptimized group (lymphoma, pneumonia, severe local reaction at the injection site, and bacteremia by Escherichia coli, 1 each). Moreover, the mean ADA treatment costs were lower in the optimized group than in the nonoptimized group (6101.25 euros/patient/year vs. 12 339.48; P < 0.01). CONCLUSION ADA optimization in BD uveitis refractory to conventional therapy is effective, safe, and cost-effective.

Etanercept-induced hypertriglyceridemia during the treatment of recurrent aphthous stomatitis.

Sir, Tumor necrosis factor alpha (TNF‐α) is known to play an important role in the lipid homeostasis.[1] However, the effects of TNF‐α inhibition on circulating lipids remain controversial.[2] In this regard, a case of hypertriglyceridemia (HTG) associated with the soluble TNF‐α receptor etanercept in a patient with psoriasis has recently been reported.[3] The HTG was also described in psoriasis patients following treatment with the anti‐TNF‐α monoclonal antibodies, such as infliximab[4] and adalimumab.[5] We report a new case of etanercept‐induced HTG during treatment of recurrent aphthous stomatitis (RAS). A 34‐year‐old non‐obese man presented with a 15‐year history of recalcitrant recurrent aphthous stomatitis (RAS). Eight to ten new recurrent lesions occurred every 2 weeks. They healed without scarring in approximately 12 days. They were very painful (subjective pain severity of 8; scale, 1‐10) and caused dysphagia. Treatment with topical and systemic corticosteroids only yielded slight improvement of symptoms. Previous treatments, such as tetracyclines, acyclovir, sulfones, colchicines, and thalidomide, had to be discontinued due to lack of efficacy or intolerance. Different conditions that may present with RAS such as Behçet ́s disease, gastrointestinal disorders, nutritional deficiencies, human immunodeficiency virus, and herpes simplex virus infection were excluded. In February 2010, he started the treatment with etanercept (25 mg twice weekly). Before the onset of this therapy, complete laboratory studies such as lipid profile and chest X‐ray did not show abnormalities. The tuberculin skin test shows negative. Significant clinical improvement was observed after 4 weeks of etanercept therapy. However, a routine blood test revealed high triglyceride (TG) levels (291 mg/dl; normal <200). After eight weeks of treatment, the TG levels rose to 529 mg/dl; high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL) cholesterols were within normal ranges. There was no family history of hyperlipidemia, diabetes, or other predisposing factors known to influence lipid metabolism.