Clinical, histologic and prognostic features of clinically amyopathic dermatomyositis.

OBJECTIVES: To characterise clinical amyopathic dermatomyositis (CADM) from a clinical, histological, and prognostic perspective. METHODS: We retrospectively recorded data from our DM cohort. Patients were categorised into three groups: classic DM, hypomyopathic DM (HDM), characterised by normal muscle strength and evidence of muscle involvement in laboratory tests and/or instrumental examinations and CADM, featured by normal muscle strength and unremarkable findings in both laboratory tests and instrumental examinations. Available muscle biopsies from each group were also compared. RESULTS: Our cohort included 63 DM (69.2%), 12 HDM (13.2%) and 16 CADM (17.6%) patients. Compared to DM, CADM patients were younger at onset and diagnosis (45.5±17 vs. 57±18, and 46±17 vs. 58±18 years, respectively; p<0.05). They were more likely to test positive for anti-MDA5 (37.5% vs. 4.8%) and anti- TIF1-γ (31.3% vs. 6.3%), had a higher incidence of arthritis (37.5% vs. 12.6%) and interstitial lung disease (ILD) (43.8% vs. 15.9%) (all comparisons with p<0.05). Muscle biopsies were available for 44 DM, 7 CADM, and 11 HDM patients, revealing similar sarcolemma MHC-I expression rates. Five-year survival rates were comparable across groups (DM: 74.6%, CADM: 75%, HDM: 83.3%). Cox analysis indicated the main mortality predictors in overall cohort were ILD (HR: 3.57, CI: 1.11-11.5) and cancer (HR: 3.67, CI: 1.17-11.5), not CADM (HR: 1.46, CI: 0.33-6.68). CONCLUSIONS: CADM patients differ in disease onset, autoantibody profiles, joint and lung involvement. While laboratory and instrumental tests have not shown muscle involvement in CADM, many muscle biopsies have shown MHC-I overexpression.

Anti-SAE dermatomyositis: clinical and histologic characteristics from a monocentric Italian cohort.

OBJECTIVES: Multiple myositis-specific antibodies have been identified, each associated with different clinical subsets of dermatomyositis (DM). Anti-SAE associated DM is considered the least studied subset. Our study aimed to evaluate the clinical and histological characteristics of DM patients with anti-SAE antibodies. As reference, patients with anti-Mi2 antibodies associated DM, representing a well-characterised subset, were analysed. METHODS: We recorded data from our DM cohort in the INflammatory MYositis REgistry (INMYRE). Patients were divided into two groups: those positive for anti-SAE and those positive for anti-Mi2 antibodies. Clinical characteristics, including skin, muscle, and extra-muscular involvements, were recorded. Available muscle biopsies were compared between the two groups. RESULTS: Of 92 DM patients, 10 (10.9%) were positive for anti-SAE and 17 (18.5%) for anti-Mi2. Anti-SAE positive DM patients showed classic DM findings but were characterised by a higher prevalence of skin itching (60% vs. 11.8%, p<0.01), shawl sign (40% vs. 5.9%, p<0.05) and lung involvement (30% vs. 0%, p<0.05) compared to anti-Mi2 positive patients. Furthermore, anti-SAE positive DM patients showed lower creatine kinase levels than those with anti-Mi2 (median [IQR]: 101 [58-647] vs. 1984 [974-3717], p<0.05) and a lower percentage of muscle fibre degeneration and necrosis (1.5%±1.7 vs. 5.9%±3.2, p<0.05) in muscle biopsies. No other differences were observed. CONCLUSIONS: Anti-SAE DM represents a disease subset characterised by classic cutaneous involvement often associated with itching, less severe muscle involvement, but potential pulmonary involvement that should always be investigated in these patients.

Perivascular and endomysial macrophages expressing VEGF and CXCL12 promote angiogenesis in anti-HMGCR immune-mediated necrotizing myopathy.

OBJECTIVES: To study the phenotype of macrophage infiltrates and their role in angiogenesis in different idiopathic inflammatory myopathies (IIMs). METHODS: The density and distribution of the subpopulations of macrophages subsets (M1, inducible nitric oxide+, CD11c+; M2, arginase-1+), endomysial capillaries (CD31+, FLK1+), degenerating (C5b-9+) and regenerating (NCAM+) myofibres were investigated by immunohistochemistry in human muscle samples of diagnostic biopsies from a large cohort of untreated patients (n: 81) suffering from anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (anti-HMGCR)+ immune mediated necrotizing myopathy (IMNM), anti-signal recognition particle (anti-SRP)+ IMNM, seronegative IMNM, DM, PM, PM with mitochondrial pathology, sporadic IBM, scleromyositis, and anti-synthetase syndrome. The samples were compared with mitochondrial myopathy and control muscle samples. RESULTS: Compared with the other IIMs and controls, endomysial capillary density (CD) was higher in anti-HMGCR+ IMNM, where M1 and M2 macrophages, detected by confocal microscopy, infiltrated perivascular endomysium and expressed angiogenic molecules such as VEGF-A and CXCL12. These angiogenic macrophages were preferentially associated with CD31+ FLK1+ microvessels in anti-HMGCR+ IMNM. The VEGF-A+ M2 macrophage density was significantly correlated with CD (rS: 0.98; P: 0.0004). Western blot analyses revealed increased expression levels of VEGF-A, FLK1, HIF-1α and CXCL12 in anti-HMGCR+ IMNM. CD and expression levels of these angiogenic molecules were not increased in anti-SRP+ and seronegative IMNM, offering additional, useful information for differential diagnosis among these IIM subtypes. CONCLUSION: Our findings suggest that in IIMs, infiltrating macrophages and microvascular cells interactions play a pivotal role in coordinating myogenesis and angiogenesis. This reciprocal crosstalk seems to distinguish anti-HMGCR associated IMNM.

Long-term efficacy of adding intravenous immunoglobulins as treatment of refractory dysphagia related to myositis: a retrospective analysis.

OBJECTIVE: Dysphagia is a life-threating manifestation of idiopathic inflammatory myopathies (IIM). However, we lack a univocal protocol for its treatment. The aim of this retrospective analysis was to evaluate the effectiveness of a step-up strategy by adding a 1-day pulse of IVIGs to immunosuppressants in IIM patients with refractory dysphagia diagnosed by Eating Assessment Tool (EAT)-10 and fibreoptic endoscopic evaluation of swallowing (FEES). METHODS: Dysphagia was defined as a pharyngo-oesophageal disturbance associated with EAT-10 score ≥3 and at least one FEES abnormality among propulsion failure, solid or liquid stasis. Eighteen out of 154 IIM patients had FEES-confirmed dysphagia and underwent 1 day IVIG 2 g/kg repeated 1 month apart for 3 months, because of dysphagia refractory to high-dose glucocorticoids with methotrexate and/or azathioprine. Clinical characteristics along with myositis-specific antibodies and muscle histopathological findings were studied in FEES-dysphagia IIM and IIM control patients. RESULTS: After three monthly doses of IVIG, EAT-10 score dropped with complete recover of defective propulsion and progressive decrease in percentage of both solid and liquid stasis. At 52-weeks' follow-up, reached in 12 patients, all these parameters were stable or further improved. An improvement in manual muscle strength test and a steroid-sparing effect of IVIG were also observed. Anti-PM/Scl 75/100 antibodies were much more frequent in the FEES-dysphagia group, while anti-Jo1 antibody was rarely detected. CONCLUSION: Our treatment schedule with 2 g/kg IVIG was effective for IIM-associated refractory dysphagia assessed by the combination of EAT-10 and FEES. These findings need to be prospectively tested in a larger cohort of IIM patients.

Severe muscle damage with myofiber necrosis and macrophage infiltrates characterize anti-Mi2 positive dermatomyositis.

OBJECTIVE: The aim of our study was to investigate clinical and histopathological findings in adult DM patients positive for anti-Mi2 (anti-Mi2+) antibodies compared with DM patients negative for anti-Mi2 (anti-Mi2-). METHODS: Clinical data of adult DM patients, who fulfilled EULAR/ACR 2017 classification criteria, were gathered from electronic medical records of three tertiary Rheumatology Units. Histopathological study was carried out on 12 anti-Mi2+ and 14 anti-Mi2- muscle biopsies performed for diagnostic purpose. Nine biopsies from immune mediated necrotizing myopathy (IMNM) patients were used as control group. RESULTS: Twenty-two anti-Mi2+ DM [90.9% female, mean age 56.5 (15.7) years] were compared with 69 anti-Mi2- DM patients [71% female, mean age 52.4 (17) years]. Anti-Mi2+ patients presented higher levels of serum muscle enzymes than anti-Mi2- patients [median (IQR) creatine-kinase fold increment: 16 (7-37)vs 3.5 (1-9.9), P <0.001] before treatment initiation. Moreover, a trend towards less pulmonary involvement was detected in anti-Mi2+ DM (9.1% vs 30.4%, P =0.05), without any case of rapidly progressive interstitial lung disease. At muscle histology, anti-Mi2+ patients showed more necrotic/degenerative fibres than anti-Mi2- patients [mean 5.3% (5) vs 0.8% (1), P <0.01], but similar to IMNM [5.9% (6), P >0.05]. In addition, the endomysial macrophage score was similar between anti-Mi2+ and IMNM patients [mean 1.2 (0.9) vs 1.3 (0.5), P >0.05], whereas lower macrophage infiltration was found in anti-Mi2- DM [mean 0.4 (0.5), <0.01]. CONCLUSIONS: Anti-Mi2+ patients represent a specific DM subset with high muscle damage. Histological hallmarks were a higher prevalence of myofiber necrosis, endomysial involvement and macrophage infiltrates at muscle biopsy.

Long-term Hodgkin Lymphoma Survivors: A Glimpse of What Happens 10 Years After Treatment.

INTRODUCTION: This retrospective study was focused on 96 patients (median age at diagnosis, 35 years) with newly diagnosed Hodgkin lymphoma (HL) treated at the University Hospital of Bari (Italy) between 2005 and 2008, to evaluate the outcome and the long-term toxicity. PATIENTS AND METHODS: First-line chemotherapy was ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in all patients; 49 (51%) patients had undergone radiotherapy. At the end of treatment, 75 (78%) patients were in complete remission (CR); 18 (24%) of 75 patients relapsed after first-line treatment; 20 (21%) underwent autologous hematopoietic stem cell transplantation, and 3 (3%) underwent allogeneic stem cell transplantation. RESULTS: After a median follow-up of 12 years, 85 (88%) patients are alive in CR, and 11 (14%) have died (2 of a second neoplasia, 1 of infection, and 8 of the disease). The 140-month Kaplan-Meier survival estimates were 86%. Three women became pregnant and each gave birth to a healthy child. The most prevalent chronic conditions at last follow-up were: a reduction in lung transfer factor for carbon monoxide (40%), fatigue (31%), hypothyroidism (30%), and infertility (16%). CONCLUSIONS: Results of this study offer indications about how long after the initial treatment excess deaths from causes other than HL begin to occur. However, challenges remain, namely establishing the optimal time to begin screening for potential late complications and developing better surveillance guidelines. Further work is needed to identify risk factors that may predict specific late effects.

Autophagy markers LC3 and p62 accumulate in immune-mediated necrotizing myopathy.

INTRODUCTION: The molecular mechanism of immune-mediated necrotizing myopathy (IMNM) remains unknown. Autophagy impairment, described in autoimmune diseases, is a key process in myofiber protein degradation flux and muscle integrity and has not been studied in IMNM. METHODS: Muscle biopsies from patients with IMNM (n = 40), dermatomyositis (DM; 24), polymyositis (PM; 8), polymyositis with mitochondrial pathology (4), sporadic inclusion body myositis (8), and controls (6) were compared by immunohistochemistry. RESULTS: The proportions of myofibers containing autophagy markers LC3b and p62 were higher in IMNM than in DM or PM and correlated with creatine kinase levels. In IMNM, compartmentalized LC3b puncta were located in regenerating and degenerating myofibers surrounded by major histocompatibility complex type II+ inflammatory cells. Several IMNM myofibers accumulated ubiquitin and misfolded protein. DISCUSSION: The detection of LC3b+ or p62+ myofibers could be used in differentiating IMNM from PM. The identification of autophagy-modifying molecules potentially could improve patients' outcomes. Muscle Nerve, 2019.

Extralymphatic Disease Is an Independent Prognostic Factor in Hodgkin Lymphoma.

PURPOSE: To identify the characteristics and outcomes of patients with extralymphatic Hodgkin lymphoma. PATIENTS AND METHODS: We performed a retrospective single-institution study of 341 cases comprising 207 male (61%) and 134 female (39%) subjects with a median follow-up of 44 months. RESULTS: Fifty-five patients (16%) had extralymphatic disease. The sites were lung in 29 patients (44%), bone in 22 (33%), liver in 12 (18%), and kidney in 3 (5%). In 46 patients (86%) only one organ was involved, while in 7 patients (13%) extralymphatic disease was present in 2 sites and in 2 patients (3%) in 3 sites. The extralymphatic disease group had a poorer prognosis than the lymphatic disease group. Complete remission rates in the extralymphatic and lymphatic patient subsets were 65% and 82% (P = .043), respectively. CONCLUSION: Extralymphatic disease in patients with Hodgkin lymphoma is a rare occurrence (16%) associated with poor clinical outcome.

Gastrointestinal bleeding as presentation of small bowel metastases of malignant melanoma: Is surgery a good choice?

INTRODUCTION: Melanoma shows a particular predilection in involving small intestine both in a single site and in multiple localization and acute or chronic gastrointestinal bleedings are often the first sign of tumour. PRESENTATION OF CASE: We report two cases of GI metastases of malignant melanoma, one presented with only a big mass that cause intestinal obstruction and the other with a tumour spread throughout the small intestine that produce enterorrhagia. DISCUSSION: Diagnosis and follow-up are very difficult: CT scan, PET-CT scan and capsule endoscopy should be complementary for the assessment of patients with GI symptoms and melanoma history. CONCLUSION: What is the role of surgery? Several studies suggest metastasectomy to achieve both R0 results and palliative resolutions of acute symptoms, such as obstruction, pain, and bleeding.

Idiopathic adult colo-colonic intussusception: Case report and review of the literature.

INTRODUCTION: Acute colonic intussusception occurring in the absence of organic cause is uncommon in adults. PRESENTATION OF CASE: We report acute colonic intussusception in a 46-year-old female; clinical evidence of a palpable mass, abdominal pain and bloody mucoid stools appeared a few hours after hospital admission. Multislice CT-scan confirmed the clinical diagnosis and surgical exploration revealed right colonic obstruction caused by intussusception of the cecum into the ascending colon. Right hemicolectomy was performed and histopathological examination did not reveal any causative pathology. DISCUSSION: Intussusception remains a rare condition in adults, representing 1-5% of bowel obstruction and accounting for 0.003-0.02% of all hospital admissions. Intussusception occurs more frequently in the small (50-80%) than in the large bowel (12-50%). It is estimated that approximately 90% of intussusceptions in adults are secondary to an anatomical or pathological condition, of which more than half are malignant. Idiopathic cases are the exception in adults. The clinical presentation of adult intussusception differs considerably from the classic pediatric presentation of abdominal pain, palpable mass, and blood per rectum, which is rarely seen in adults. A pre-operative CT-scan showed a 10cm intussuscepted segment of right colon. Surgical resection was considered mandatory because of severe bowel obstruction, and the theoretical possibility of occult malignancy. This approach was vindicated by the presence of widespread ischemic lesions in the wall of the resected bowel, without any obvious lead point. CONCLUSION: There are few reports in the medical literature of acute colonic intussusception occurring in the absence of organic cause in adults.

Splenic localization of the peritoneal mesothelioma: case report and literature revue.

Peritoneal mesothelioma is a rare form of malignant mesothelioma, making up <30% of diagnosed mesothelioma cases. Because of a lack of specific symptoms (abdominal pain, abdominal swelling), normally it is diagnosed in advanced stages, sometimes in a surgical emergency (intestinal obstruction, severe ascites) and occasionally during image procedures or laparoscopy which can show a mass developing from peritoneal mesothelium surfaces, or an accumulation of small irregularities that may be tumors or plaques. The reported case refers to a particular localization of a peritoneal mesothelioma, the spleen, discovered only after a splenectomy, due to the clinical and radiological suspect of a rupture.

Massive gastrointestinal bleeding due to splenotic nodule of the gastric wall. A case report.

Splenosis results from autotransplantation of splenic tissue after traumatic splenic rupture or surgery. Usually asymptomatic, splenosis is an incidental finding at surgery, unrelated to the splenosis, for intestinal obstruction or suspected appendicitis or gynaecological pathology. This article describes a unique case of massive gastrointestinal bleeding caused by deep invasion of a splenotic nodule into the gastric wall.

[Acute appendicitis: is this common pathology still of interest?]. / Appendicite acuta: c'è acora interesse per una patologia così comune?

Despite the indisputable progress of technology (laboratory analyses, scintigraphy, ultrasonography, computed tomography), the diagnosis of acute appendicitis often remains uncertain, with a rate of useless appendectomies amounting to almost 20% of cases. The ideal diagnostic test has yet to be discovered and, in any case, clinical observation remains the cornerstone of any decision-making algorithm. Thus, acute appendicitis continues to offer food for thought in relation to the aetiology of the condition, which is still unknown, the primacy of the clinical diagnosis, and the learning of the surgical skills required. In the present study, the authors compare their personal experience with the relevant data in the international literature, emphasising a number of issues such as the problem of diagnosis, acute appendicitis in pregnancy, laparoscopic therapy, and the so-called "useless appendectomies" and presenting their own point of view.

Small bowel obstruction due to intramural hematoma during anticoagulant therapy. With regard to two cases treated conservatively.

Hemorrhage following prolonged oral anticoagulant administrations is a well recognized hazard of therapy, and hemorrhagic complications are said to occur in 10-30% of patients. Following the presentation of the cases, the authors examine the current literature concerning the problems with anticoagulants, and recommend models of diagnosis and treatment of complications by bowel obstruction. Authors report on two cases of small bowel obstruction due to intramural hematoma during anticoagulant therapy. It is extremely important to recognize this syndrome in order to avoid unnecessary operative intervention. Therefore, laparotomy is not indicated.