Guido Massi

Clinically silent inflammatory gut lesions in undifferentiated spondyloarthropathies

SummaryGastrointestinal inflammation or infection can be associated with various forms of arthritis, such as, acute reactive arthritis triggered by enteritis due to gram-negative bacteria or ankylosing spondylitis and peripheral arthritis in relation to Crohns disease and ulcerative colitis. Using colonoscopy, we have found a high prevalence of clinically silent inflammatory lesions in 38 patients (24 males and 14 females) affected by undifferentiated spondyloarthropathies (SpA). Microscopic inflammatory lesions were present in all the patients. Three patterns of nonspecific chronic inflammatory alterations were observed. No difference was noted between patients taking or not taking nonsteroidal anti-inflammatory drugs. Direct immunofluorescence demonstrated the presence of IgG, IgA, IgM, C3, C4 and fibrinogen in 75% of the specimens examined. The finding of chronic inflammatory gut lesions hypothesizes that a local activation of the immune system depending on the persistence of intestinal microbial antigens or toxins, due to impaired elimination or increased exposition, may have a part in the pathogenesis of SpA.

Interstitial granulomatous dermatitis in rheumatoid arthritis responsive to etanercept

Interstitial granulomatous dermatitis (IGD) is a rare dermatological condition presenting as erythematous plaques. It may be associated with drug-related adverse reactions and autoimmune diseases. Recent cases of IGD have been reported in rheumatoid arthritis (RA) patients treated with biologic agents. We report a case of RA patient with persistent erythematous plaques who did not respond to traditional disease-modifying anti-rheumatic drugs with a persistent skin condition of erythematous plaque eruptions. A biopsy showed a homogeneous inflammatory infiltrate in the deep dermis composed of large epithelioid histiocytes with occasional granulocytes, leading us to consider a diagnosis of IGD. The cutaneous lesions disappeared after a 3-month treatment with the tumour necrosis factor-α (TNF-α) inhibitor etanercept. Anti-TNF-α agents can antagonise the multiple effects of TNF-α on the immune system, effects that are required for the continued maintenance of granulomatous structure, and offer a therapeutic strategy in the treatment of IGD associated with arthritis.

Characterization of alpha-1-antitrypsin by isoelectric focusing on an ultrathin polyacrylamide gel layer

SummaryThrough the use of ultrathin layer polyacrylamide gel isoelectric focusing it is possible to obtain a resolution of the bands of α1AT so as to be able to easily recognize all six PiM subtypes. The optimal resolution of the PiM subtypes is obtained without deforming the pattern of the Pi phenotypes. In addition to high resolution, ultrathin layer polyacrylamide gel isoelectric focusing permits a notable reduction of fees to 1/5 of the usual.

Alpha-1-antitrypsin phenotypes in a group of newborn infants in Somalia

SummaryPi phenotype determinations were performed on umbilical cord serum specimens of 347 infants born in Mogadishu (Somalia) hospitals. Phenotyping was performed by isoelectric focusing on polyacrylamide gel slabs. Sera containing α1AT in types other than MM were also studied by crossed antigen-antibody immunoelectrophoresis on agar.The most frequently occuring Pi allele proved to be PiM. With respect to the other African populations studied so far, there was a high prevalence of the PiS and PiZ alleles. In particular, three individuals were found with the ZZ phenotype, which had not yet been observed in Africa.

A Fast Amplification-Reverse Hybridization Assay Kit to Detect the Most Frequent Deficient Variants in the Alpha-1-Antitrypsin Gene

Background: There is worldwide growing awareness of alpha-1-antitrypsin deficiency (AATD), a major hereditary disorder in Caucasians. The gold standard for its laboratory diagnosis is thin-layer isoelectric focusing, which should be performed in reference laboratories. Objectives: The aim of this study was to check the characteristics of a commercially available amplification-reverse hybridization assay kit in detecting at a molecular level the alpha-1-antitrypsin (AAT) Z and S variants, i.e. the most frequent variants associated with AATD, by comparing its performance with DNA restriction fragment length polymorphism. Methods: We studied samples from 36 subjects enrolled in the Italian National Registry for Severe Alpha-1-antitrypsin Deficiency. Based on previous plasma isoelectric focusing typing, we selected samples with the following phenotypes: MM (9 samples), MS (9 samples), SZ (3 samples), MZ (11 samples), ZZ (3 samples), and a rare variant (1 sample). DNA was extracted by the standard method. The presence of the AAT Z and S gene variants was determined by the amplification-reverse hybridization test kit, following the manufacturer’s instructions, and by the restriction fragment length polymorphism technique, according to established procedures. Results: We found that the identification of the AAT Z and S gene variants obtained by the amplification-reverse hybridization test kit was completely in agreement with that obtained by the restriction fragment length polymorphism technique. Conclusions: We conclude that the test kit provides a fast, easy and unambiguous identification of Z and S alleles. Because of its transferability to routine laboratories, the test kit may be useful in identifying cases of severe AATD, thus resulting in increasing awareness of this rare disorder.

Alpha-1-antitrypsin (?1AT) phenotypes and PiM subtypes in Italy. Evidence of considerable geographic variability

SummaryGenetic typing of α1AT was performed in 3751 individuals from Italian towns. The following was observed: (a) The pathologic phenotypes (SZ, MZ, ZZ) appeared to decrease progressively from northern to southern Italy; (b) the distribution of the PiM suballeles showed considerable geographic variability, but the suballele, M2 was more frequently encountered in southern Italy; and (c) in the large cities of southern Italy, the frequency of the deficiency more closely resembled that found in northern Italy than that of the remaining populations of the south.

Lymphoepithelioma-like carcinoma of the skin.

The term lymphoepithelioma-like carcinoma identifies a group of nasopharingeal epithelial tumors characterized by aggregates of malignant undifferentiated cells surrounded by a dense reactive lymphoplasmacellular infiltrate. Primary cutaneous localization is rare, with approximately 30 cases reported in literature. We describe a case of primary lymphoepithelioma-like carcinoma of the skin in a 92-year-old woman. Immunohistochemical examination was positive for cytokeratine (KL1 and EMA) as regards epithelial cells, while the lymphocitic infiltrate was positive for LCA and CD3. In situ hybridization for Epstein Barr virus in tumor cells was negative. Electron microscopy showed rounded and occasionally spindle-shaped poorly-differentiated squamous epithelial cells, and a lymphoid stroma consisting mostly of normal-appearing small lymphocytes. Examination of the nasopharynx did not show any tumoral mass and after a 7 years follow-up the patient is free of local and distant recurrences. This tumor affects people aged over 50 years and is localized to the face, but scalp, shoulder and forearm may be involved. Research of Epstein-Barr virus is always negative in this tumor, unlike nasopharingeal epithelial carcinoma. The differential diagnosis of lymphoepithelioma-like carcinoma of the skin may present some difficulties and includes squamous cell carcinoma. Lymphoepithelioma-like carcinoma of the skin is a malignant neoplasm which tends to relapse locally and has a moderate tendency to metastatize.

Protein absorption by tubular mesonephric and metanephric structures in the human embryo

SummaryThe presence of different serum proteins in the cells of the proximal tubule of both meso- and metanephric nephrons in human embryos (7th–12th week of intrauterine life) was investigated using immunohistochemistry. Endogenous lysozyme, alpha-1-antitrpysin and ferritin were detected in mesonephric proximal tubules and, starting from the 8th week, also in metanephric proximal tubules. Our observations provide information concerning the appearance and distribution of tubular protein reabsorption during the early stages of development.

Updated review of the pathogenesis and management of Merkel cell carcinoma

Background: Merkel cell carcinoma is a rare, aggressive, malignant cutaneous tumor of the elderly or immunosuppressed individuals that usually appears on sun-exposed areas of the body. Its pathogenesis is still debated, and, currently, no standardized treatment exists. Objective: To provide a current updated review of the most relevant data concerning the pathogenesis and management of Merkel cell carcinoma. Methods: Using relevant MeSH terms, we performed a review of the literature on these subjects from 1980 to June 2009. Results and Conclusion: The current management of Merkel cell carcinoma is based on surgical excision as the majority of patients present with localized disease, whereas up to 30% have regional lymph node metastases. In these cases, the best outcome is achieved with multidisciplinary management that includes radiotherapy. Chemotherapy is part of the treatment in advanced cases and is mandatory for distant metastatis. Given that a recent work showed the presence of a previously unknown polyomavirus, which the authors called Merkel cell polyomavirus, the therapeutical approach to Merkel cell carcinoma could be reconsidered in the future.

Circumscribed pityriasis rubra pilaris type IV

A 23-year-old woman presented with a hyperkertotic erythematous plaque on her left thigh. It had appeared 5 years previously, and its appearance and size had remained stable. She was in good health and had no other medical problems. There was no family history of dermatological disorders. On physical examination, a single plaque on the posterior region of the left thigh was seen. It was erythematous, slightly scaly and with islands of noninvolved skin within the affected area (Fig. 1). The lesion was accompanied by slight itching. Nails, hair, mucosa, palms and soles showed no changes. Laboratory investigations, including complete blood cell count and serum chemistry were normal. Serological testing for human immunodeficiency virus (HIV) was negative.