Claudio Guarneri

Helicobacter pylori and autoimmune pancreatitis: role of carbonic anhydrase via molecular mimicry?

Autoimmune pancreatitis is a recently defined nosological entity, which accounts for 4.6‐6% of all forms of chronic pancreatitis and is often associated with other autoimmune diseases, particularly Sjögrens syndrome. Possession of the HLA DRB1*0405‐DQB1*0401 genotype confers a risk for the development of autoimmune pancreatitis. Autoantibodies against carbonic anhydrase II and lactoferrin are frequently present in affected subjects and are suspected to have a pathogenic role. A link between gastric infection by Helicobacter pylori and autoimmune pancreatitis has been hypothesized. We used in silico protein analysis and search for HLA binding motifs to verify this hypothesis. We found a significant homology between human carbonic anhydrase II and α‐carbonic anhydrase of Helicobacter pylori, an enzyme which is fundamental for the survival and proliferation of the bacterium in the gastric environment. Moreover, the homologous segments contain the binding motif of the HLA molecule DRB1*0405. Our data strengthen the hypothesis that gastric Helicobacter pylori infection can trigger autoimmune pancreatitis in genetically predisposed subjects.

Identification of potentially cross-reactive peanut-lupine proteins by computer-assisted search for amino acid sequence homology.

Background: Allergic cross-reactions are an issue of major concern because of implications for public health. The molecular basis of cross-allergy is the similarity of epitopes belonging to proteins of different organisms. Lupine is an emerging cause of food allergy, which has become a ‘hot topic’ because of recent large-scale introduction into processed foods and frequent cross-reactions with other members of the legume family. However, no lupine allergen has been characterized thus far. Prompted by a recently reported case of peanut-lupine cross-allergy, we wished to identify the possible cross-reactive allergen(s) between the two vegetal species. Methods: We used computer-aided amino acid sequence comparison, a well-established technique for the study of protein homology, and followed the FAO/WHO guidelines for the identification of potential allergens. We also performed a three-dimensional modeling of the suspected cross-reactive proteins to compare their molecular surfaces. Results: We found a highly significant sequence homology and molecular similarity between allergen Ara h 8 of peanut and pathogenesis-related protein PR-10 of white lupine. Another protein of lupine, the β-conglutin precursor, was found to be significantly homologous to the Ara h 1 allergen of peanut. The molecular surfaces of Ara h 8 and PR-10 were remarkably similar. Conclusions: Our in silico data allow to predict the allergenicity of PR-10 and β-conglutin precursor of white lupine according to FAO/WHO guidelines. Amino acid sequence homology also suggests that these proteins could be responsible, at least in part, for some of the allergic cross-reactions between peanut and lupine reported in the literature.

Immunogenicity of anti-TNFα therapy in psoriasis: a clinical issue?

Introduction: Immunogenicity of antitumor necrosis factor-alpha (TNFα) agents has been proven to play a significant role in the variability of clinical responses among patients with chronic inflammatory diseases. However, its clinical impact on the outcome of patients with psoriasis and psoriatic arthritis receiving anti-TNFα treatment is not yet fully clear. Despite the high rates of efficacy of anti-TNFα agents in psoriasis, a substantial proportion of patients remain who experience a primary or secondary failure or significant side effects, which are potentially ascribable to immunogenicity. Areas covered: Topics include immunologic response elicited by anti-TNFα agents, the impact of immunogenicity on treatment response to anti-TNFα and the role played by immunogenicity in the lack of efficacy of anti-TNFα agents (infliximab, adalimumab and etanercept) in psoriasis. Expert opinion: Based on data available in the literature and the clinical experience of the authors, this article suggests the optimal approach to drug monitoring and antidrug antibody assay and the most effective use of biologic immunotherapies in this setting. Immunogenicity should be taken into account in the adoption of therapeutic choices in psoriatic patients, such as anti-TNFα agent intensification, or switching to another anti-TNFα agent or a drug with a different mechanism of action.

Cross‐reactivity of Anisakis simplex: possible role of Ani s 2 and Ani s 3

Background  Anisakis simplex is a fish parasite that can cause allergy in humans. The multiple cross‐reactivities of this nematode make diagnostic tests for allergy unreliable, because of frequent false‐positive results. To date, only four allergens of A. simplex have been characterized, but their role in cross‐reactivity is largely unknown.

Efficacy and Safety of Systemic Treatments for Psoriasis in Elderly Patients

Management of psoriasis in elderly patients can be challenging, because of the impairment of immune system efficiency and the presence of comorbidities that contra-indicate systemic therapies. We studied the safety and efficacy of systemic traditional and biological treatments in 187 consecutive psoriatic patients aged > 65 years. At week 12 of therapy, Psoriasis Area and Severity Index 75 was achieved by 49%, 27%, 46% and 31% of patients who received methotrexate, acitretin, cyclosporine or PUVA, and 64.1%, 64.7%, 93.3%, 57.1% and 100% of patients who received etanercept, adalimumab, infliximab, efalizumab and ustekinumab. The rate of adverse events was 0.12, 0.32, 1.4 and 0.5 per patient-year in the methotrexate, acitretin, cyclosporine and PUVA groups and 0.11, 0.35, 0.19, 0.3 and 0.26 in the etanercept, adalimumab, infliximab, efalizumab and ustekinumab groups. Traditional drugs were less effective than biologics in our elderly population. Etanercept was associated with a lower rate of adverse events compared with other treatments.

Emerging targeted therapies for melanoma treatment (Review)

Cutaneous melanoma is an aggressive cancer with a poor prognosis for patients with advanced disease. The identification of several key molecular pathways implicated in the pathogenesis of melanoma has led to the development of novel therapies for this devastating disease. In melanoma, both the Ras/Raf/MEK/ERK (MAPK) and the PI3K/AKT (AKT) signalling pathways are constitutively activated through multiple mechanisms. Targeting various effectors of these pathways with pharmacologic inhibitors may inhibit melanoma cell growth and angiogenesis. Ongoing clinical trials provide hope to improve progression-free survival of patients with advanced melanoma. This review summarizes the most relevant studies focused on the specific action of these new molecular targeted agents. Mechanisms of resistance to therapy are also discussed.

Subcutaneous fat necrosis of the newborn: Be aware of hypercalcaemia

Abstract:  Subcutaneous fat necrosis of the newborn is an uncommon, self‐limiting panniculitis that usually occurs in full‐term infants as a consequence of perinatal asphyxia. The cutaneous involvement may be associated with metabolic complications such as hypoglycaemia, thrombocytopenia, hypertriglyceridemia, anemia and hypercalcaemia. The delayed onset of hypercalcaemia, 1–6 months after the development of the skin manifestations, imposes a prolonged follow‐up to avoid its acute toxic effects on cardiovascular and renal systems and the more durable metastatic calcifications.

Nicolau Syndrome Following Etanercept Administration

Nicolau syndrome (NS), or embolia cutis medicamentosa, is a well-known but rare adverse effect of a still largely unidentified pathogenesis, observed primarily after the intramuscular administration of various drugs. NS is characterized by immediate excruciating pain, early pallor and erythema and oedema at the injection site, followed by cutaneous, subcutaneous and even muscular aseptic necrosis in a livedoid pattern. It is a potentially serious reaction that is little influenced by which drug is injected.A case is reported of NS following a subcutaneous self-injection of etanercept for psoriasis and psoriatic arthritis. This case is remarkable because NS developed after subcutaneous and not after intramuscular drug administration, and because no cases of NS following the injection of tumour necrosis factor alpha inhibitors have been reported in the literature or in the World Health Organization adverse drug reactions database. Although not directly linked to the drug, the occurrence of NS has to be considered in patients receiving biological agents.

Mucosal Leishmaniasis Occurring in a Renal Transplant Recipient

The long-term use of immunosuppressive therapy in transplant recipients causes a well-known high susceptibility to opportunistic infections. Several cases of visceral leishmaniasis have been reported in immunosuppressed patients; cutaneous and, especially, mucosal involvement has rarely been described in the literature. We report a case of mucosal leishmaniasis, occurring in a renal transplant recipient, observed in Sicily, an endemic region for the Leishmania infantum. A 65-year-old white man, a farm labourer, was referred to our department because he had had, for 4 months, a painless, rapidly growing, infiltrating lesion localised in the lower lip. At the age of 59, he had received an orthotopic renal transplant for focal sclerosing glomerulonephritis and was started on cyclosporine A and methylprednisolone for immunosuppression. He had no history of cutaneous disease. He had never travelled out of Italy. Physical examination revealed a hard, diffuse enlargement of the left half of the lower lip, partially covered by small scabs (fig. 1a); granulomatous changes were visible on the internal side of the cheek (fig. 1b). There were no palpable lymph nodes, and no other lesions were noted on the body. Histology of two biopsy specimens, respectively from the vermilion area and the cheek, showed a dense dermal inflammatory cell infiltrate composed of lymphocytes and histiocytes. In the cytoplasm of the latter, numerous Leishman-Donovan bodies were present. Routine laboratory tests were within the normal ranges; human immunodeficiency virus (HIV) 1 and HIV-2 testing, serum venereal disease research laboratory and Leishmania serology performed by immunofluorescence were negative, as well as culture in NovyMcNeal-Nicolle medium. A bone marrow biopsy specimen was negative for Leishmania. The diagnosis of mucosal leishmaniasis was based upon history and histopathological examination, revealing Leishmania amastigotes in the dermis. Differential diagnosis, including trauma, fixed drug eruption, syphilitic chancre, Melkersson-Rosenthal syndrome, granulomatous cheilitis, sarcoidosis and lymphoedema, were excluded on the basis of anamnestic, clinical and laboratory data.

Cutaneous angiosarcoma of the face

Cutaneous angiosarcoma is a rare tumour of vascular origin, which has a poor prognosis because of its high potential for metastasis. We report the case of a 57‐year‐old man with an 8‐month history of a progressively enlarging, asymptomatic red patch over the left periorbital region of the face, previously diagnosed as angiolupoid leishmaniasis, insect‐bites, ‘cellulitis’ and treated with several topical antibiotic and steroid therapy, without any improvement. A skin biopsy of the lesion was performed and histological and immunohistochemical examination revealed a pattern of poorly differentiated angiosarcoma. The peculiarity of the localization at the periorbital area and the particular clinical presentation are emphasized.