Iago Pinal-Fernández

Diagnosis and classification of eosinophilic fasciitis.

Eosinophilic fasciitis (EF) is a rare scleroderma-like syndrome with an unknown etiology and pathogenesis that should be considered an immune-allergic disorder. Painful swelling with progressive induration and thickening of the skin and soft tissues of the limbs and trunk are the clinical hallmarks of the disease. Peripheral blood eosinophilia, hypergammaglobulinemia, and elevated erythrocyte sedimentation rate are the main laboratory findings. Full-thickness wedge biopsy of the clinically affected skin showing inflammation and thickening of deep fascia is essential to establish the diagnosis. The differential diagnosis includes systemic sclerosis and other scleroderma subsets such as morphea, and epidemic fasciitis syndromes caused by toxic agents such as the myalgia-eosinophilia syndrome and toxic oil syndrome. Peripheral T cell lymphomas should also be ruled out. The diagnosis of EF can be established by clinical, laboratory and histological findings, but universally accepted international diagnostic criteria are lacking. Corticosteroids are efficacious and remain the standard therapy for EF, although some patients may improve spontaneously.

IgG4-related disease: Evidence from six recent cohorts.

IgG4-related disease (IgG4-RD) is a rare autoimmune fibrosing disorder. In this review we aim to describe and compare the characteristics of the six largest IgG4-RD cohorts, since the new 2012 consensus diagnostic criteria were released. These observational studies were published between 2012 and 2015. Patients were included using the comprehensive diagnostic criteria or the 2012 consensus criteria. Results were reviewed and summarized. Most patients were middle aged men. Fibro-inflammatory masses developed in virtually all organs except the brain, with an unexplained preference for salivary glands, lymph nodes and pancreas. Corticosteroids were the treatment of choice but up to 40% of patients relapsed within the first year. Standardized response assessment tools, biomarkers and the validation of new treatments are still in development. In conclusion, the features of IgG4-RD are similar across the globe. At the moment, corticosteroids are the only validated treatment but rituximab seems to be promising.

Statin-associated autoimmune myopathy: A distinct new IFL pattern can increase the rate of HMGCR antibody detection by clinical laboratories.

BACKGROUND AND OBJECTIVE Statin-associated autoimmune myopathy (SAAM) with anti-HMGCR antibodies has recently been described. Several specific immunoassays are in use to detect HMGCR antibodies. In the course of systematic autoantibody screening we recognized a new distinct IFL staining pattern on rat liver sections that regularly coincided with anti-HMGCR antibodies. In this study we investigated whether this new IFL pattern is specifically associated to statin-associated autoimmune myopathy and corresponds to anti-HMGCR antibodies. PATIENTS AND METHODS Twenty-three patients positive for anti-HMGCR antibodies (14 diagnosed with SAAM) were investigated for anti-HMGCR antibodies by two ELISA assays and confirmed by immmunoblot. HMGCR associated liver IFL pattern (HALIP) was detected by indirect IFL and the reactivity against HMGCR was confirmed by immunoabsorption using purified human HMGCR antigen. 90 patients with other autoimmune diseases and 45 non-autoimmune statin treated patients were studied as controls. RESULTS 21 out of 23 (91%) anti-HMGCR positive patients were HALIP positive. The staining was completely and specifically removed by immunoabsorption with human purified HMGCR. None of the control sera from autoimmune patients or non-autoimmune statin treated subjects was positive for HALIP. Statistical concordance between HALIP and anti-HMGCR antibody specific tests was 98.7%, kappa 0.95. CONCLUSIONS A new and distinct IFL staining pattern (HALIP) is associated to HMGCR associated myopathy. Absorption and concordance studies indicate that the antigen recognized in the liver by HALIP is HMGCR or a closely related protein. Awareness of this new pattern can help to detect HMGCR autoantibodies in statin treated patients tested for autoimmune serology.

Histiocytoid Sweet syndrome and cutaneous polyarteritis nodosa secondary to myelodysplastic syndrome

Dear Editor, In 1964 R.D. Sweet described a clinical picture affecting young women, characterized by fever, neutrophilia, raised plaques in the limbs, face and neck and a dense neutrophilic infiltrate quickly reversed with corticosteroids. This corresponded to the classical form of Sweet syndrome (SS), by far the most common variant (80–90% of cases), but pharmacological, gestational or paraneoplastic types of SS have been described, representing the hematologic neoplasms the 85% of the latter group, which has specific clinical and epidemiological characteristics: no female predominance, elderly patient affectation, relapsing clinical course, atypical lesions and frequent extracutaneous involvement. On the other hand, histiocytoid SS (HSS), a histologic variant of SS characterized by a mononuclear histiocytoid infiltrate, was described by Requena et al. in 2005. Additionally, in 1931, Lindberg first recognized cutaneous polyarteritis nodosa (cPAN), a rare form of vasculitis of unknown etiology limited to skin, affecting small-to-medium-sized arteries. We report a patient with HSS and cPAN, both secondary to a myelodysplastic syndrome (MS). A 75-year-old patient presented with a history of polymyalgia rheumatica 5 years before admission, idiopathic pleuropericarditis 3 years before, prostate neoplasm successfully treated with radiation and hormone therapy 1 year before and fluctuating leukopenia, thrombocytopenia and anemia of unknown origin during the last 6 years, with no transfusion requirements until the time of admission. The patient requested a second opinion in our center because of recurrent episodes over the last year of fever (39°C), arthralgias and slightly burning, maculo-papular, erythematous, sharp-edged lesions, affecting arms, face, abdomen and back, with a previous biopsy showing a monocytic infiltrate in superficial and deep dermis. The patient was treated with corticosteroids (prednisone 0.3–0.5 mg/kg/day), initially with a good response, but recurrence when prednisone was tapered below 0.2 mg/ kg/day. For this reason other immunosuppressive drugs (azathioprine and cyclophosphamide) were added to the treatment without improvement. On admission, the patient reported the appearance of sporadic nodules in the anterior and lateral lower extremities over the last 2 years, usually unilateral, of sudden onset and gradual spontaneous resolution, leading to mild residual hyperpigmentation, with previous biopsies showing an intense inflammatory infiltrate in the hypodermis and deep dermis affecting medium vessel walls, associated with segmental areas of fibrinoid necrosis. Physical examination revealed residual nodular lesions in the anterior surface of the legs, and maculopapular lesions on the back, arms and abdomen, scarcely representative. Fever of 39°C and a flare of cutaneous lesions developed immediately after the withdrawal of corticosteroids (Fig. 1). However, the leg nodules remained unchanged.

Inflammatory myopathy: diagnosis and clinical course, specific clinical scenarios and new complementary tools

Idiopathic inflammatory myopathies are a heterogeneous group of rare autoimmune diseases characterized by symmetric proximal muscle weakness and inflammatory infiltrates on muscle biopsy. A meticulously collected combination of clinical, serological, and pathological data is essential to correctly diagnose and classify myositis patients, often a considerable challenge for clinicians. This article provides a comprehensive overview of the most useful tools for the diagnosis and follow-up of patients with myositis. Capillaroscopy, serological biomarkers (particularly the autoantibody profile) and imaging techniques, such as muscle magnetic resonance and chest ultrasound, are of great aid in diagnosing, classifying and managing these patients. Relevant clinical scenarios, such as interstitial lung disease, associated cancer and pregnancy are also addressed in this review. Myositis registries, identification of new autoantibodies, and genetic studies will enhance our understanding of the pathogenesis of these conditions and help to define new diagnostic and therapeutic approaches.

Statins and myositis: the role of anti-HMGCR antibodies

Muscle toxicity is a recognized adverse effect of statin use. Recently, a new myositis syndrome was described in association with antibodies directed against the pharmacologic target of statins, anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR antibody). The patient’s genetic background, characteristic histologic patterns (immune-mediated necrotizing myopathy), and presence of anti-HMGCR antibodies define the syndrome. In most patients, statin discontinuation is insufficient to reverse the myositis symptoms, and immunosuppressive therapy is needed. The mechanisms by which these antibodies may lead to disease are not fully elucidated. Several important questions remain unsolved and warrant further research.

RIG-I expression in perifascicular myofibers is a reliable biomarker of dermatomyositis

BackgroundDermatomyositis (DM) is inflammatory myopathy or myositis characterized by muscle weakness and skin manifestations. In the differential diagnosis of DM the evaluation of the muscle biopsy is of importance among other parameters. Perifascicular atrophy in the muscle biopsy is considered a hallmark of DM. However, perifascicular atrophy is not observed in all patients with DM and, conversely, perifascicular atrophy can be observed in other myositis such as antisynthetase syndrome (ASS), complicating DM diagnosis. Retinoic acid inducible-gene I (RIG-I), a receptor of innate immunity that promotes type I interferon, was observed in perifascicular areas in DM. We compared the value of RIG-I expression with perifascicular atrophy as a biomarker of DM.MethodsWe studied by immunohistochemical analysis the expression of RIG-I and the presence of perifascicular atrophy in 115 coded muscle biopsies: 44 patients with DM, 18 with myositis with overlap, 8 with ASS, 27 with non-DM inflammatory myopathy (16 with polymyositis, 6 with inclusion body myositis, 5 with immune-mediated necrotizing myopathy), 8 with muscular dystrophy (4 with dysferlinopathy, 4 with fascioscapulohumeral muscle dystrophy) and 10 healthy controls.ResultsWe found RIG-I-positive fibers in 50% of DM samples vs 11% in non-DM samples (p < 0.001). Interestingly, RIG-I staining identified 32% of DM patients without perifascicular atrophy (p = 0.007). RIG-I sensitivity was higher than perifascicular atrophy (p < 0.001). No differences in specificity between perifascicular atrophy and RIG-I staining were found (92% vs 88%). RIG-I staining was more reproducible than perifascicular atrophy (κ coefficient 0.52 vs 0.37).ConclusionsThe perifascicular pattern of RIG-I expression supports the diagnosis of DM. Of importance for clinical and therapeutic studies, the inclusion of RIG-I in the routine pathological staining of samples in inflammatory myopathy will allow us to gather more homogeneous subgroups of patients in terms of immunopathogenesis.

Lung transplantation in systemic sclerosis: A single center cohort study

OBJECTIVE Lung transplantation (LT) has been proposed as a treatment for advanced interstitial lung disease (ILD) and/or pulmonary hypertension (PH) associated to systemic sclerosis (SSc) but few studies have been reported. The aim of this study was to describe the clinical features, complications and survival of a single-center cohort of patients with SSc that underwent LT and to compare their survival with a group of non-SSc transplanted patients. METHODS Fifteen patients with SSc were transplanted between May 2005 and April 2015. Standard international criteria were used to determine eligibility for LT. The severity of gastroesophageal involvement was not considered as a major contraindication if symptoms were under control. RESULTS Eight (53.3%) patients had diffuse cutaneous SSc. Eleven (73%) underwent bilateral LT. The main indication for LT was ILD, with or associated PH in 4 cases. Acute cellular rejection and infections were the most frequent complications. Functional lung tests tended to keep stable after transplantation. Median survival was 2.4 years (Q1-Q3: 0.7-3.7 years). We did not find differences in survival between patients transplanted with SSc versus those transplanted due to non-SSc ILD or PH. SSc complications were scarce with no patient developing PH after LT. CONCLUSIONS LT was an effective treatment for advanced ILD and/or PH associated to SSc in our study. Gastroesophageal reflux was not a limitation for LT in SSc in this study. Complications and survival did not differ from non-SSc patients undergoing LT.

High‐resolution manometry in patients with idiopathic inflammatory myopathy: Elevated prevalence of esophageal involvement and differences according to autoantibody status and clinical subset

In this study we assessed high‐resolution manometry (HRM) findings in patients with dermatomyositis and polymyositis.

OP0009 Distinctive Immunofluorescence Pattern in Statin-Associated Autoimmune Myopathy with Anti-HMGCR Autoantibodies

Background A statin-associated autoimmune myopathy with anti-HMGCR antibodies has recently been described. Identification of these patients is of paramount importance because immunosuppressive therapy is usually needed for clinical improvement. Herein we report a new pattern of immunofluorescence (IIF) that could alert of the presence of this antibody in routine autoantibody screening on kidney, liver, stomach sections. Objectives Our objective was to study the concordance of this IIF pattern with anti-HMGCR in a series of patients with immune-mediated necrotizing myopathy (IMNM). Methods Seventeen patients diagnosed with IMNM positive for anti-HMGCR antibodies were tested for the presence of IIF pattern. As a control group, 90 patients diagnosed with systemic autoimmune diseases (SLE, autoimmune hepatitis, systemic sclerosis, rheumatoid arthritis, Sjögren syndrome, and dermatomyositis – 15 from each group), and 45 patients treated with statins (15 with familial severe dyslipidemia, 15 with a recent cerebrovascular event – treated high dose of atorvastatin, and 15 from the community) were also studied. Anti-HMGCR antibodies were measured by means of two ELISA assays: a in-house confirmed by blot using hidroxi-methil-glutharil-CoA (Sigma H7039) as antigen and commercial QUANTA Lite HMGCR ELISA Innova (San Diego). Indirect immunofluorescence studies on triple tissue (rat liver, kidney and stomach) was performed using Nova Lite assay (Innova Diagnostic, San Diego, USA). We used different commercial substrates (Innova, Euroimmune, ByoSistems, and Aeskulides) in order to confirm that the reactivity of the pattern do not depend on the commercial source. Indirect immunofluorescence on HEp-2 Slides (INOVA Diagnostics, Inc., San Diego Hep-2 ANA slides) was also performed. Immunoabsorption studies were performed using HMGCR human antigen (Sigma, St Louis, MO,USA) at different dilutions (PBS 10%) in those patients with a positive IIF pattern Results A cytoplasmatic pattern in scattered hepatocytes with perivascular distribution was observed in 15 out of 17 (88%) IMNM positive for anti-HMGCR antibodies. No patients from the autoimmune systemic disease group or those treated with statins disclosed this characteristic pattern. Consequently, the overall agreement between rat triple tissue IIF and ELISA confirmed by blot was 98.7% (kappa 0.93). Dispersed hepatocyte cytoplasmatic pattern (DHCP) was specifically absorbed by incubation with human purified antigen. A granular cytoplasmatic fluorescence pattern was observed in 6 out of 17 (35%) patients with human Hep cells. Conclusions A new distinctive IIF pattern on routine rat triple tissue is described in patients diagnosed with IMNM whit anti-HMGCR antibodies. It could be useful to alert of the presence of anti-HMGCR antibodies when performing a routine unexpensive autoantibody profile. Disclosure of Interest None declared