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Marzia Caproni

Publications and source records attributed to Marzia Caproni.

28 records · Page 2Linked to original sources
PubMed2002

Th1, Th2 and Th3 cytokines in the pathogenesis of bullous pemphigoid.

Bullous pemphigoid (BP) is an autoimmune bullous skin disease mediated by autoantibodies against hemidesmosomal proteins. In addition to humoral immunity, the contribute of infiltrating T-helper (Th) autoreactive lymphocytes and their related cytokines to the pathomechanism of blistering is now growing in interest. To investigate T-cell activation markers and the presence of inflammatory and fibrogenic cytokines (i.e. IL2, IL-4, IL-5, IFN-gamma, TGF-beta) in BP lesional skin, we performed an immunohistochemical study and an in situ hybridization procedure on five BP patients, comparing them with two psoriatic patients and four healthy subjects. Our aim was to expand suitable information about tissutal expression of cytokines, secondly to further investigate the role of TGF-beta (a Th3-like or T-regulatory (T-reg) cytokine) in a non-scarring disorder like BP, in order to highlight its pleiotropic activity. The immunohistochemical analysis revealed a moderate to strong staining for IL-4 and IL-5 with a prevalent perivascular localization in the upper dermis. The staining for IFN-gamma showed a moderate/focal expression on the dermal perivascular infiltrate. IL-2 protein was observed in four cases. While no positive staining for IL-4 mRNA was detected in all BP subjects with in situ hybridization, IL-5 mRNA was documented in four BP specimens. A focal nuclear staining for IFN-gamma was observed in the epidermal layers and on the cellular infiltrate of lesional skin. In all BP cases, a moderate/diffuse positivity for TGF-beta(1) mRNA was documented in both cytoplasm and nucleus of the infiltrating perivascular cells of lesional and perilesional skin. Our results suggest a balance between Th1, Th2 and Th3 activity, with quantitatively different impact of the various cytokines on the pathomechanism of blistering, depending on the reciprocal network. The supposed participation of each cytokine analyzed in the pathogenesis of BP is discussed. The newest data obtained consist of TGF-beta detection in a non-scarring disease like PB, that had never been documented before, and in the confirmation of a mixed cytokine pattern in the fully developed phase of the disease.

Aged↗
PubMed2002

IL-4, IL-5, TGF-beta1 and IFN-gamma mRNAs detected by a new in situ amplification system in cicatricial pemphigoid.

The process that induces chronic progressive scarring in cicatricial pemphigoid (CP), a rare group of autoimmune mucocutaneous blistering diseases, is still under investigation. The tendency to heal with scar formation observed in CP could be due to the specific localization of the antigen in the basement membrane zone or could depend on the frequent recurrence of the disease in a localized area. The release of soluble fibrogenic factors by inflammatory infiltrating cells has also been considered as pathogenetically relevant. The aim of this study is to evaluate the expression of mRNA for IL-4, IL-5, TGF-beta1, IFN-gamma in patients with CP, and investigate the role of the cytokine profile as a possible cause of the clinical features and course of the disease. Fourteen patients (3 male, 11 female; age range 40-72 years) with oral (n = 10), preputial (n = 3) and cutaneous (n = 1) CP were studied. The formalin-fixed and paraffin-embedded biopsies were examined by in situ hybridization performing a new amplification system based on biotinyl-tyramide. As a control, 4 patients (2 male, 2 female; age range 58-73 years) affected by bullous pemphigoid (BP), the most common autoimmune subepidermal blistering disease, were also examined. In CP, IL-4 mRNA expression was present in 4 out of the 14 cases analysed. IL-5 was detected in 12 CP biopsies. TGF-beta1 and IFN-gamma mRNAs were identified in 9 and 11 CP cases, respectively. In BP, an IL-4 hybridization signal could not be observed in any of the cases. By contrast IL-5, TGF-beta1 and IFN-gamma mRNA analyses were positive in all four BP cases. Our results suggest the presence of a T-cell population with a mixed cytokine pattern in the cellular infiltrate of both blistering diseases, with a corresponding increase of Th2-like activity in fully developed lesions, irrespective of the different sites involved. In addition, on the basis of the constant presence of TGF-beta1 mRNA in the different lesional phases of CP, and its overlapping expression in BP, we hypothesize that the involvement of additional factors is responsible for the scarring course typical of CP.

Adult↗
PubMed2002

Serum eosinophil cationic protein, myeloperoxidase, tryptase, eotaxin and Th2-L-like cytokines in Dermatitis herpetiformis.

BACKGROUND: Dermatitis herpetiformis (DH) is a subepidermal bullous disease characterized by a neutrophilic and eosinophilic infiltrate, together with activated lymphocytes that show preferential polarization towards the Th2-like phenotype. To date, the role of neither soluble mediators, such as cytokines, nor serum levels of myeloperoxidase (MPO), eosinophil cationic protein (ECP) and tryptase (TRY) have been studied in the peripheral blood of DH. In this study we investigated 40 DH subjects for possible alterations in MPO, ECP, TRY, eotaxin, interleukin (IL) 4 and IL-5 concentrations to evaluate the role of neutrophils, eosinophils and mast cells in the induction of skin lesions. Sera from 20 healthy subjects were tested as controls. METHODS: Eotaxin, IL-4 and IL-5 serum contents were determined by a solid-phase enzyme-linked immunosorbent assay. A double antibody radioimmunoassay was used to measure serum levels of MPO, ECP and TRY. RESULTS: Normal levels of eotaxin and IL-4 were found in all DH subjects; increased IL-5 levels were found only in 1 subject. The MPO levels were significantly higher in DH subjects than in healthy controls (p < 0.01). There was also a significant difference between the serum ECP levels of DH and healthy controls (p < 0.05). TRY was not revealed in the serum of DH subjects. CONCLUSIONS: The determination of Th2-like cytokines and TRY serum levels is not important in quantifying the involvement of activated lymphocytes and mast cells in DH; however, the finding of high MPO and ECP serum levels seems to confirm that these products are good markers of the presence of activated neutrophils and eosinophils.

Adolescent↗
PubMedDate not supplied

Case study: pachyonychia congenita: a mixed type II-type IV presentation.

A 52-year-old woman in good health with a family history negative for dermatologic diseases presented to our department with thickening and dystrophy of all her fingernails and toenails that started when she was born. She also had hyperkeratosis on the palms of her hands and soles of her feet that was confined to sites of pressure and recurrent plantar blisters that began appearing at puberty. The patient reported marked pain while walking from such plantar involvement. Her medical history revealed a persistent hoarseness; palmoplantar hyperhidrosis; and the appearance of numerous cysts on her back, neck, and scalp since she was 20 years old. These latter lesions had been diagnosed as multiple steatocystoma on the basis of the histologic features. Upon examination, all of her fingernails and toenails appeared shortened, thickened,and dystrophic (Figures 1-3). In addition, they presented subungual keratosis and a yellowish-gray color. Hyperkeratosis and small ulcerations were present on the perionychium. Palmoplantar keratoderma was evident, especially on the soles,in association with superficial erosions (Figure 4). Keratosis pilaris was evident on the extensor surfaces of the forearms as well as on the anterior surfaces of the legs. Multiple nodules were detected on the patient's neck, trunk, and axillary regions(Figure 5). They consisted of multiplex steatocystoma and were characterized by a hemispheric shape, a normal-appearing skin color, and by an elastic consistency on palpation. Oral and dental changes were not detected, although hair anomalies were evident. Laboratory parameters disclosed eosinophilia and increased total IgE levels. The results of serum protein electrophoresis was normal, as were those concerning hepatic and renal functions. The ophthalmology examination showed neither corneal dyskeratosis nor cataracts. The neurologic-psychiatric visit revealed slight mental retardation.

Diagnosis, Differential↗
PubMedDate not supplied

Systemic lupus erythematosus with unusual maculopapular and erosive cutaneous lesions.

In 2002, a 38-year-old woman was referred to the department of dermatological sciences for the evaluation of erythematous-infiltrated lesions with prominent purpuric and erosive components distributed on her face, upper chest, and extensor surfaces of the limbs, which developed over a 3-month period. In 1997 the patient suffered from polyarthralgia (proximal interphalangeal,knee, wrist, and metacarpophalangeal joints) associated with morning stiffness. In 1999 she was admitted to a psychiatric unit for depression with episodes of lipothymia. In the same year, since she developed diffuse and persistent urticarial manifestations with angioedema and livedo reticularis of the limbs in association with anticardiolipin antibodies, vasculitis was proposed. Upon examination, erythematous-infiltrated and erosive lesions in association with serohemorrhagic crusts were present on the face,neck, chest, upper trunk, and extensor surfaces of the upper limbs and thighs (Figures 1-3). Telangiectasias were especially evident on the cheeks, where prominent edema conferred her face a moon-like appearance (Figure 1). Laboratory investigations disclosed microcytic anemia, elevated erythrocyte sedimentation rate, proteinuria (30 mg/dL), positive antinuclear antibodies (1:80) with diffuse fluorescence pattern, lowered complement levels (C3: 31 mg/dL, C4: 3 mg/dL), circulating immunocomplexes binding Clq, and high titers of anti-TSH receptor antibodies. Indirect immunofluorescence was negative for the detection of anti-basement membrane zone antibodies. Histological examination of the lesional skin of the shoulder documented epidermal atrophy, marked vacuolar degeneration of the basal cell layer, colloid bodies, and a perivascular lymphohistiocytic infiltration of the upper and deep dermis (Figure 4). Direct immunofluorescence performed on affected skin showed junctional granular deposition of IgG, C3,and Clq in association with perivascular C3 and Clq deposits in the upper dermis; direct immunofluorescence on sun-protected,non-lesional skin showed similar immunological deposition both at the basement membrane zone and in the perivascular dermis.Based upon the clinical, histologic, and immunopathologic findings, we proposed the diagnosis of systemic lupus erythematosus with maculopapular and erosive skin lesions. The patient was treated with methylprednisolone IV (pulse therapy, 250 mg) tapered over 10 days and later continued p.o. After a few weeks, significant improvement of cutaneous manifestations was noted.

Adult↗
PubMedDate not supplied

Case study: periodic follow-up is necessary in morphea profunda to identify systemic evolution.

The term "morphea" includes a wide spectrum of clinical entities, varying from localized plaques of only cosmetic importance to deep lesions resulting in considerable morbidity for the patient. In fact, although survival rates are no different from that of the general population, localized scleroderma may be associated with development of substantial disability, as occurs in deep morphea and in pediatric patients (disabling pansclerotic morphea of children). We report a case of morphea profunda affecting a young man with severe, rapidly progressive, widespread skin involvement and focus on the eventual systemic evolution of such cases. A 40-year-old man was admitted in 2002 for progressive subcutaneous indurations, preferentially involving the right side of the trunk. His health was altogether good, with the exception of a beginning chronic obstructive bronchopneumopathy. There was no family or personal history of dysmetabolic, cardiovascular, neoplastic, or cutaneous disease. Three years earlier, the patient had noted the appearance of two infiltrated, intensely red lesions on the right laterocervical and paraumbilical regions. These had been interpreted as subcutaneous lipomatosis on the basis of an ultrasound scan. The lesions had become progressively larger, while their surface had assumed a scleroatrophic appearance. Thereafter, other lesions had developed on his chest and lower limbs, mostly distributed on the right side of the body. Clinical examination revealed well demarcated, depressed sclerotic plaques with ivory-colored centers and erythematous borders ("lilac ring") localized on the neck, chest, and lower abdomen and limbs (Figure 1). They were bound to the deeper structures and arranged in a band-like linear distribution on the right side of the chest and abdomen where they extended horizontally for more than 10 cm in diameter. These lesions were totally asymptomatic. In addition, arborizing telangiectasias were evident on the neck and upper chest (Figure 2). Laboratory investigations provided normal range of erythrocyte sedimentation rat and C reactive protein levels and other inflammation markers. Antinuclear antibody, antidouble-strand DNA, antimitochondrial, anti-extractable antigens (anti-centromere, anti-Scl-70, anti-U1RNP), and anti-Borrelia burgdorferi antibodies were negative. Circulating immunocomplexes binding C1q were substantially increased. Oesophageal x-rays and lower limb electromyography were within normal limits; ventilatory function testing revealed a mild obstruction consistent with the beginning of chronic obstructive pulmonary disease. Although nailfold capillaroscopy documented nonspecific findings of connective tissue disease (mega-capillaries, segmentary dilatation and destruction), the laser-Doppler flussimetry revealed few signs of microcirculatory abnormalities, in absence of Raynaud's phenomenon. An abdominal wall ultrasonography, performed on a sclerotic plaque, documented thinning of the subcutaneous tissue, with increase of the fibrous component and lower fascia and muscle retraction. The biopsy specimen from the abdominal region included fascia and the subcutaneous tissue (previously obtained from the lower abdomen) with epidermal atrophy, a thickening and homogenization of collagen bundles in the deep dermis and hair reduction. A perivascular lympho-monocytic and plasmacellular infiltration with a dermo-epidermal distribution was present. Moreover, septal fibrosis with a perivascular lymphoplasmacellular inflammatory infiltrate was documented within the abdominal rectus muscle. The diagnosis of morphea profunda was made on the basis of clinical and histopathological findings. A therapeutic regimen based on amino benzoic potassium (Potaba; Glenwood, LLC, Glenwood, NJ), oral prednisone, and topical clobetasol was started. After several months of follow-up, the patient had obtained only moderate improvement of the clinical findings.

Adult↗