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Papers by Annalisa Arlotta
The Lancet Rheumatology, 2021
Summary Background Presenting symptoms of childhood cancers might mimic those of rheumatic diseas... more Summary Background Presenting symptoms of childhood cancers might mimic those of rheumatic diseases. However, the evidence available to guide differential diagnosis remains scarce. Preventing wrong or delayed diagnosis is therefore important to avoid incorrect administration of glucocorticoid or immunosuppressive therapy and worsening of prognosis. As such, we aimed to assess the prevalence and characteristics of presenting musculoskeletal manifestations in patients at cancer onset and to identify the factors that differentiate childhood malignancies with arthropathy from juvenile idiopathic arthritis. Methods We did a multicentre, cross-sectional study at 25 paediatric haemato-oncology centres and 22 paediatric rheumatology centres in Italy. We prospectively recruited patients who were younger than 16 years that were newly diagnosed with cancer or juvenile idiopathic arthritis. We excluded patients with glucocorticoid pre-treatment (>1 mg/kg per day of oral prednisone or equivalent for ≥2 consecutive weeks). We collected data for patients with a new diagnosis of cancer or juvenile idiopathic arthritis using an electronic case report form on a web-based platform powered by the Cineca Interuniversity Consortium. The primary outcome was to describe the frequency and characteristics of musculoskeletal manifestations at cancer onset; and the secondary outcome was to identify factors that could discriminate malignancies presenting with arthropathy, with or without other musculoskeletal symptoms, from juvenile idiopathic arthritis using multivariable logistic regression analysis. Findings Between May 1, 2015, and May 31, 2018, 1957 patients were eligible, of which 1277 (65%) had cancer and 680 (35%) had juvenile idiopathic arthritis. Musculoskeletal symptoms occurred in 324 (25% [95% CI 23·0–27·8]) of 1277 patients with cancer, of whom 207 had arthropathy. Patients with malignant bone tumours had the highest frequency of musculoskeletal symptoms (53 [80%] of 66), followed by patients with Langerhans histiocytosis (16 [47%] of 34), leukaemia (189 [32%] of 582), soft-tissue sarcomas (16 [24%] of 68), and neuroblastoma (21 [19%] of 109). In the 324 patients with cancer and musculoskeletal symptoms, the most common complaints were joint pain (199 [61%]), followed by limb bone pain (112 [35%]). Joint involvement had a prevalent monoarticular pattern (100 [48%] of 207) and oligoarticular pattern (86 [42%] had 2–4 joints involved and 20 [10%] had >4 joints involved), with the most frequently involved joints being the hip (88 [43%] of 207) and knee (81 [39%]). On multivariable analysis, limb bone pain was the independent variable most strongly associated with cancer (odds ratio [OR] 87·80 [95% CI 18·89–408·12]), followed by weight loss (59·88 [6·34–565·53]), thrombocytopenia (12·67 [2·40–66·92]), monoarticular involvement (11·30 [4·09–31·19]), hip involvement (3·30 [1·13–9·61]), and male sex (2·40 [1·03–5·58]). Factors independently associated with juvenile idiopathic arthritis were morning stiffness (OR 0·04 [95% CI 0·01–0·20]), joint swelling (0·03 [0·01–0·09]), and involvement of the small hand joints (0·02 [0–1·05]). Interpretation Our study provides detailed information about presenting musculoskeletal manifestations of childhood cancers and highlights the clinical and laboratory features that are most helpful in the differential diagnosis with juvenile idiopathic arthritis. Funding Associazione Lorenzo Risolo.
European review for medical and pharmacological sciences, 2012
In patients with chronic congenital haemolytic disorders, human Parvovirus B19 (HPV B19) is frequ... more In patients with chronic congenital haemolytic disorders, human Parvovirus B19 (HPV B19) is frequently involved in pure red-cell aplastic crises. Furthermore, it may inhibit three-lineage haematopoiesis in the bone marrow, causing severe pancytopenia. In such patients, Epstein Barr virus (EBV) infection also seems to share the same mechanism as HPV B19 in inducing bone marrow aplasia, but at present the clinical effect of an infection sustained by both viruses is unknown. We present a 7-year-old boy affected by hereditary spherocytosis (HS) who suffered from transient aplastic crisis, in whom laboratory findings revealed a double HPV B19 and EBV infection. To our knowledge, this is the first report of a case of HPV B19 and EBV co-infection diagnosis in a paediatric patient. Despite underlying HS, no signs of haemolytic anaemia were detected, but the infection only produced transient pancytopenia. Nevertheless, the reason why there was no additive effect of the two viruses on the apl...
La Pediatria medica e chirurgica : Medical and surgical pediatrics
Gliomas currently represent a group of uncommon diseases originating from glial elements. Accordi... more Gliomas currently represent a group of uncommon diseases originating from glial elements. According to their biologic features they can be distinguished in low-grade gliomas--not very aggressive and with a poor tendency to progression--and high-grade gliomas--with a greater proliferative drive and aggressiveness. Such definitions outline two distinct disease types, which profoundly differ as for epidemiological, clinical, diagnostic and molecular features. The introduction of biomolecular techniques has provided a deeper knowledge of low-grade gliomas: the use of new molecular markers, such as Ki-67, makes it possible to study peculiar features of the neoplasm, with strong prognostic implications. Nonetheless, in the literature there is still no agreement on their role, nor on their prognostic validity in pediatric age, also because the criteria that are currently used for adult patients haven't still been codified for pediatric age.
Pediatric Blood & Cancer, 2009
We present three cases of children (aged 3-5 years) in which cancer-related pain was adequately c... more We present three cases of children (aged 3-5 years) in which cancer-related pain was adequately controlled by Transdermal Buprenorphine. The endpoints for evaluating analgesic efficacy consisted of the assessment of pain using a visual scale and the possibility of reducing other pain treatment. Improvement of pain level was demonstrated by the decrease in pain scores, by reduction of the overall amount of medications, especially opioids, and by improvement of uninterrupted sleep. Only limited data is available on the use of Transdermal Buprenorphine in children. In our experience, Transdermal Buprenorphine allowed good analgesia without significant side effects in these three children with cancer-related pain.
Journal of Pediatric Hematology/Oncology, 2011
Gastric adenocarcinoma is rare in childhood and often presents with disseminated malignancy at di... more Gastric adenocarcinoma is rare in childhood and often presents with disseminated malignancy at diagnosis due to aspecific symptoms leading to delay in diagnosis. A familial predisposition for gastrointestinal cancer is suggested for the development of this early-onset adenocarcinoma. We report the case of a 14-year-old girl with a familial history of colorectal, liver, and breast cancers affected by metastatic gastric adenocarcinoma, who first presented with thrombotic microangiopathy. Thrombotic microangiopathy as first clinical presentation of metastatic gastric cancer is an exceptional event in childhood and represents a challenge for pediatricians. Gastric adenocarcinoma should be suspected in young patients with a significant familial history and also in the absence of initial specific signs, so as to provide correct diagnosis and appropriate treatment.
Journal of Pediatric Hematology/Oncology, 2014
Nontuberculous mycobacterial infections are rare but severe complications of chemotherapy in chil... more Nontuberculous mycobacterial infections are rare but severe complications of chemotherapy in children. In children with prolonged lymphopoenia after mieloablative regimens, symptoms can be nonspecific and fever and pulmonary impairment are the most common clinical features. Diagnosis is challenging for physicians and microbiologists and often requires invasive techniques. We report a girl affected by acute lymphoblastic leukemia, who developed a disseminated infection sustained by Mycobacterium avium complex. Identification of the microorganism was obtained by open lung biopsy and evidence of mycobacterium genome. We also reviewed 15 literature cases of disseminated infections of nontuberculous mycobacterium in children with leukemia.
Haematologica, 2006
Recently, rare CD4+/CD56+ hematodermic neoplasm has been described as a distinct clinico-patholog... more Recently, rare CD4+/CD56+ hematodermic neoplasm has been described as a distinct clinico-pathologic entity, with aggressive course and poor outcome. Skin is typically involved at presentation, but widespread dissemination to bone marrow is rapid. To date, no standardized therapeutic approach to this disease has been established. As its diffusion mainly concerns elderly patients, only a few paediatric cases have been documented. We report an additional case of CD4+/CD56+ hematodermic tumour that showed a good response to chemotherapy based on a lymphoma protocol. Moreover, we try to analyse features and outcome of a few other paediatric CD4+/CD56+ hematodermic tumours as they are reported in the literature.
Journal of Pediatric Hematology/Oncology, 2014
Nontuberculous mycobacterial infections are rare but severe complications of chemotherapy in chil... more Nontuberculous mycobacterial infections are rare but severe complications of chemotherapy in children. In children with prolonged lymphopoenia after mieloablative regimens, symptoms can be nonspecific and fever and pulmonary impairment are the most common clinical features. Diagnosis is challenging for physicians and microbiologists and often requires invasive techniques. We report a girl affected by acute lymphoblastic leukemia, who developed a disseminated infection sustained by Mycobacterium avium complex. Identification of the microorganism was obtained by open lung biopsy and evidence of mycobacterium genome. We also reviewed 15 literature cases of disseminated infections of nontuberculous mycobacterium in children with leukemia.
The Lancet Rheumatology, 2021
Summary Background Presenting symptoms of childhood cancers might mimic those of rheumatic diseas... more Summary Background Presenting symptoms of childhood cancers might mimic those of rheumatic diseases. However, the evidence available to guide differential diagnosis remains scarce. Preventing wrong or delayed diagnosis is therefore important to avoid incorrect administration of glucocorticoid or immunosuppressive therapy and worsening of prognosis. As such, we aimed to assess the prevalence and characteristics of presenting musculoskeletal manifestations in patients at cancer onset and to identify the factors that differentiate childhood malignancies with arthropathy from juvenile idiopathic arthritis. Methods We did a multicentre, cross-sectional study at 25 paediatric haemato-oncology centres and 22 paediatric rheumatology centres in Italy. We prospectively recruited patients who were younger than 16 years that were newly diagnosed with cancer or juvenile idiopathic arthritis. We excluded patients with glucocorticoid pre-treatment (>1 mg/kg per day of oral prednisone or equivalent for ≥2 consecutive weeks). We collected data for patients with a new diagnosis of cancer or juvenile idiopathic arthritis using an electronic case report form on a web-based platform powered by the Cineca Interuniversity Consortium. The primary outcome was to describe the frequency and characteristics of musculoskeletal manifestations at cancer onset; and the secondary outcome was to identify factors that could discriminate malignancies presenting with arthropathy, with or without other musculoskeletal symptoms, from juvenile idiopathic arthritis using multivariable logistic regression analysis. Findings Between May 1, 2015, and May 31, 2018, 1957 patients were eligible, of which 1277 (65%) had cancer and 680 (35%) had juvenile idiopathic arthritis. Musculoskeletal symptoms occurred in 324 (25% [95% CI 23·0–27·8]) of 1277 patients with cancer, of whom 207 had arthropathy. Patients with malignant bone tumours had the highest frequency of musculoskeletal symptoms (53 [80%] of 66), followed by patients with Langerhans histiocytosis (16 [47%] of 34), leukaemia (189 [32%] of 582), soft-tissue sarcomas (16 [24%] of 68), and neuroblastoma (21 [19%] of 109). In the 324 patients with cancer and musculoskeletal symptoms, the most common complaints were joint pain (199 [61%]), followed by limb bone pain (112 [35%]). Joint involvement had a prevalent monoarticular pattern (100 [48%] of 207) and oligoarticular pattern (86 [42%] had 2–4 joints involved and 20 [10%] had >4 joints involved), with the most frequently involved joints being the hip (88 [43%] of 207) and knee (81 [39%]). On multivariable analysis, limb bone pain was the independent variable most strongly associated with cancer (odds ratio [OR] 87·80 [95% CI 18·89–408·12]), followed by weight loss (59·88 [6·34–565·53]), thrombocytopenia (12·67 [2·40–66·92]), monoarticular involvement (11·30 [4·09–31·19]), hip involvement (3·30 [1·13–9·61]), and male sex (2·40 [1·03–5·58]). Factors independently associated with juvenile idiopathic arthritis were morning stiffness (OR 0·04 [95% CI 0·01–0·20]), joint swelling (0·03 [0·01–0·09]), and involvement of the small hand joints (0·02 [0–1·05]). Interpretation Our study provides detailed information about presenting musculoskeletal manifestations of childhood cancers and highlights the clinical and laboratory features that are most helpful in the differential diagnosis with juvenile idiopathic arthritis. Funding Associazione Lorenzo Risolo.
European review for medical and pharmacological sciences, 2012
In patients with chronic congenital haemolytic disorders, human Parvovirus B19 (HPV B19) is frequ... more In patients with chronic congenital haemolytic disorders, human Parvovirus B19 (HPV B19) is frequently involved in pure red-cell aplastic crises. Furthermore, it may inhibit three-lineage haematopoiesis in the bone marrow, causing severe pancytopenia. In such patients, Epstein Barr virus (EBV) infection also seems to share the same mechanism as HPV B19 in inducing bone marrow aplasia, but at present the clinical effect of an infection sustained by both viruses is unknown. We present a 7-year-old boy affected by hereditary spherocytosis (HS) who suffered from transient aplastic crisis, in whom laboratory findings revealed a double HPV B19 and EBV infection. To our knowledge, this is the first report of a case of HPV B19 and EBV co-infection diagnosis in a paediatric patient. Despite underlying HS, no signs of haemolytic anaemia were detected, but the infection only produced transient pancytopenia. Nevertheless, the reason why there was no additive effect of the two viruses on the apl...
La Pediatria medica e chirurgica : Medical and surgical pediatrics
Gliomas currently represent a group of uncommon diseases originating from glial elements. Accordi... more Gliomas currently represent a group of uncommon diseases originating from glial elements. According to their biologic features they can be distinguished in low-grade gliomas--not very aggressive and with a poor tendency to progression--and high-grade gliomas--with a greater proliferative drive and aggressiveness. Such definitions outline two distinct disease types, which profoundly differ as for epidemiological, clinical, diagnostic and molecular features. The introduction of biomolecular techniques has provided a deeper knowledge of low-grade gliomas: the use of new molecular markers, such as Ki-67, makes it possible to study peculiar features of the neoplasm, with strong prognostic implications. Nonetheless, in the literature there is still no agreement on their role, nor on their prognostic validity in pediatric age, also because the criteria that are currently used for adult patients haven't still been codified for pediatric age.
Pediatric Blood & Cancer, 2009
We present three cases of children (aged 3-5 years) in which cancer-related pain was adequately c... more We present three cases of children (aged 3-5 years) in which cancer-related pain was adequately controlled by Transdermal Buprenorphine. The endpoints for evaluating analgesic efficacy consisted of the assessment of pain using a visual scale and the possibility of reducing other pain treatment. Improvement of pain level was demonstrated by the decrease in pain scores, by reduction of the overall amount of medications, especially opioids, and by improvement of uninterrupted sleep. Only limited data is available on the use of Transdermal Buprenorphine in children. In our experience, Transdermal Buprenorphine allowed good analgesia without significant side effects in these three children with cancer-related pain.
Journal of Pediatric Hematology/Oncology, 2011
Gastric adenocarcinoma is rare in childhood and often presents with disseminated malignancy at di... more Gastric adenocarcinoma is rare in childhood and often presents with disseminated malignancy at diagnosis due to aspecific symptoms leading to delay in diagnosis. A familial predisposition for gastrointestinal cancer is suggested for the development of this early-onset adenocarcinoma. We report the case of a 14-year-old girl with a familial history of colorectal, liver, and breast cancers affected by metastatic gastric adenocarcinoma, who first presented with thrombotic microangiopathy. Thrombotic microangiopathy as first clinical presentation of metastatic gastric cancer is an exceptional event in childhood and represents a challenge for pediatricians. Gastric adenocarcinoma should be suspected in young patients with a significant familial history and also in the absence of initial specific signs, so as to provide correct diagnosis and appropriate treatment.
Journal of Pediatric Hematology/Oncology, 2014
Nontuberculous mycobacterial infections are rare but severe complications of chemotherapy in chil... more Nontuberculous mycobacterial infections are rare but severe complications of chemotherapy in children. In children with prolonged lymphopoenia after mieloablative regimens, symptoms can be nonspecific and fever and pulmonary impairment are the most common clinical features. Diagnosis is challenging for physicians and microbiologists and often requires invasive techniques. We report a girl affected by acute lymphoblastic leukemia, who developed a disseminated infection sustained by Mycobacterium avium complex. Identification of the microorganism was obtained by open lung biopsy and evidence of mycobacterium genome. We also reviewed 15 literature cases of disseminated infections of nontuberculous mycobacterium in children with leukemia.
Haematologica, 2006
Recently, rare CD4+/CD56+ hematodermic neoplasm has been described as a distinct clinico-patholog... more Recently, rare CD4+/CD56+ hematodermic neoplasm has been described as a distinct clinico-pathologic entity, with aggressive course and poor outcome. Skin is typically involved at presentation, but widespread dissemination to bone marrow is rapid. To date, no standardized therapeutic approach to this disease has been established. As its diffusion mainly concerns elderly patients, only a few paediatric cases have been documented. We report an additional case of CD4+/CD56+ hematodermic tumour that showed a good response to chemotherapy based on a lymphoma protocol. Moreover, we try to analyse features and outcome of a few other paediatric CD4+/CD56+ hematodermic tumours as they are reported in the literature.
Journal of Pediatric Hematology/Oncology, 2014
Nontuberculous mycobacterial infections are rare but severe complications of chemotherapy in chil... more Nontuberculous mycobacterial infections are rare but severe complications of chemotherapy in children. In children with prolonged lymphopoenia after mieloablative regimens, symptoms can be nonspecific and fever and pulmonary impairment are the most common clinical features. Diagnosis is challenging for physicians and microbiologists and often requires invasive techniques. We report a girl affected by acute lymphoblastic leukemia, who developed a disseminated infection sustained by Mycobacterium avium complex. Identification of the microorganism was obtained by open lung biopsy and evidence of mycobacterium genome. We also reviewed 15 literature cases of disseminated infections of nontuberculous mycobacterium in children with leukemia.