Giuseppe De Panfilis

Clinical, Histological and Immunopathological Features of 58 Patients with Subacute Cutaneous Lupus erythematosus

Background: Subacute cutaneous lupus erythematosus (SCLE) is a distinct subset of cutaneous lupus erythematosus clinically characterized by psoriasiform and/or annular lesions and by a mild or absent systemic involvement. Objective: The Italian Group of Immunodermatology of the Italian Society of Dermatology and Venereology reviewed the cases of SCLE seen in 10 years (1987–1996). Patients: Forty-six women and 12 men have been retrospectively studied, 42% had annular lesions, 39% psoriasiform ones and 16% both. Results: Lesions were mainly localized on the neck and face and relapsed in spring and autumn. Seventeen patients had 4 or more American College of Rheumatology criteria and could be classified as having systemic lupus erythematosus. The most frequent histopathological alterations were epidermal atrophy, hydropic degeneration of the basal layer and perivascular lymphocytic infiltrate. Deposits of immunoglobulins and C3 at the dermo-epidermal junction on the clinically involved skin were present in 86% of the patients. Dust-like particles in the epidermis were only found in 3% of cases. Anti-Ro/SSA antibodies were found in 71% of the cases and anti-dsDNA only in 5% of cases. Conclusions: SCLE is a particular subset of cutaneous lupus erythematosus with peculiar clinical and immunopathological features.

Relapses after treatment of external genital warts are more frequent in HIV-positive patients than in HIV-negative controls

Background Recurrences of cervical lesions associated with human papillomavirus are more frequent in HIV-infected (HIV+) than in HIV− women. Recurrences of external genital warts were investigated in HIV+ patients and HIV− control subjects. Goal To compare relapses after treatment of external genital warts between HIV+ and HIV− patients. Study Design At the sexually transmitted disease (STD) center in Brescia, Italy, 1336 patients (241 HIV+ and 1095 HIV−) with external genital warts were examined in the decade 1990 to 1999. Various local treatments were used. Results Treatments generally triggered recovery from the lesions. The relapses observed up to 1 year after the response, examined by survival analysis, were significantly (P < 0.001) more frequent in the HIV+ (160 cases; 66.4%) than in the HIV− (294 cases; 26.8%) subjects. Multiple relapses observed up to 1 year after treatment occurred in 69 of 241 HIV+ patients, as compared with 14 of 1095 HIV− control subjects (P < 0.001). Conclusion According to the study findings, HIV infection can be considered a risk factor for the development and recurrence of external genital warts. Multiple relapses should drive patients to HIV testing.

Cd4+ and Cd8+ Lymphocytes of Patients with Aids Synthesize Increased Amounts of Interferon-γ

Individual cells capable of interferon-gamma (IFN-gamma) synthesis are easily detected by immunofluorescence and flow cytometric analysis using an anti-IFN-gamma monoclonal antibody as specific reagent. By IFN-gamma flow cytometry assay, we demonstrated that HIV-seropositive patients, starting at the early stage of viral infection, generally have an increased percentage of lymphocytes potentially able to produce IFN-gamma, compared with healthy blood donors. IFN-gamma expression in patient lymphocytes was observed to increase with the progressive stages of HIV infection, with the highest figures occurring in stage C patients. Such increased IFN-gamma expression involved both CD4+ and CD8+ T cell subsets. Most interestingly, we found patients at the same stage of HIV infection who had similar numbers of total and CD4+ lymphocytes but highly different percentages of lymphocytes potentially capable of producing IFN-gamma.

A reappraisal of the use of 5‐methoxypsoralen in the therapy of psoriasis

Abstract 5‐methoxypsoralen (5‐MOP) is considered an alternative to 8‐methoxypsoralen (8‐MOP) for photochemotherapy of psoriasis. We have compared the clinical efficacy and tolerability of 5‐MOP (1.2 mg/kg)‐UVA versus 8‐MOP (0.6 mg/kg)‐UVA therapy in 25 patients of skin type III and IV, affected by relapsing plaque‐type psoriasis of similar body involvement; indeed, the same patients were given 8‐MOP during 1 year and 5‐MOP during the subsequent year after relapsing. Both treatments cleared psoriatic lesions with a comparable number of exposures, but 5‐MOP required significantly higher cumulative UVA doses. The difference was due to the lower phototoxicity of 5‐MOP, as assessed by the determination of the minimal phototoxic dose, and to its higher tanning activity, as assessed by the weekly grading of pigmentation. Nevertheless, therapy by 5‐MOP‐UVA seemed particularly interesting in that it showed a higher tolerability since only 1 patient experienced nausea, whereas during therapy with 8‐MOP‐UVA nausea and/or vomiting occurred in 7 patients, sunburn in 6 and itching in 3. Since we have treated the same patients with the two drugs, our results were not influenced by interindividual variations of phototoxic responses, tanning ability and susceptibility to develop psoraleninduced short‐term side‐effects. It was concluded that, although long‐term side‐effects of the 5‐MOP‐UVA treatment have still to be determined, such treatment of psoriasis should be reappraised due to its higher tolerability in comparison to 8‐MOP‐UVA treatment.

Treatment of chronic venous leg ulcers by platelet gel

ABSTRACT:  Chronic venous leg ulcers (CVLU) are chronic wounds, associated with long‐standing venous hypertension, which have a poor prognosis for healing. In the process of wound healing the first step is represented by platelet aggregation and subsequent release of growth factors and other mediators, which play a key role in the repair response. Platelet gel (PG), a hemocomponent obtained by mixing platelets, thrombin, and calcium, is able, when applied topically, to release platelet mediators that likely favor CVLU healing. However, unstandardized protocols have been described in studies utilizing PG for the regeneration of a number of tissues, including CVLU; the relative clinical outcomes were hence highly variable. In our experience the topical use of PG, together with the strict adherence to the principles of good wound care, quickly promoted increased granulation tissue, followed by a complete CVLU epithelization. Although further studies and trials are needed to establish the major outcome affecting rules for optimal indications, preparation, and use of PG for CVLU treatment, PG can be undoubtedly considered a useful tool, able to improve the management of CVLU.

Bath-5-methoxypsoralen-UVA therapy for psoriasis

BACKGROUND After oral intake, 5-methoxypsoralen (5-MOP) is as effective as 8-MOP for PUVA therapy for psoriasis, with a lower incidence of acute cutaneous side effects. OBJECTIVE We compared bath-water delivery of 5-MOP and 8-MOP for photochemotherapy of psoriasis. METHODS Twenty-two patients underwent phototesting with 0.0003% 5-MOP or 8-MOP aqueous solutions. Twelve patients with palmar psoriasis were studied with a side-to-side comparison, and 10 patients with recurrent plaque-type psoriasis were treated with one therapy or the other. RESULTS Minimal phototoxic dose (MPD) values were 2.8 +/- 1.2 J/cm2 with 8-MOP and 2.0 +/- 1.2 J/cm2 with 5-MOP (p < 0.01). Both therapies cleared palmar lesions but 8-MOP required more UVA irradiation (46.3 +/- 21.0 J/cm2 vs 30.2 +/- 21.5 J/cm2; p < 0.01) and more exposures (21.0 +/- 6.0 vs 17.0 +/- 5.0; p = 0.02). Bath-5-MOP-UVA was also more effective in the treatment of plaque-type psoriasis (cumulative UVA doses, 56.8 +/- 39.2 vs 59.1 +/- 27.9 J/cm2; number of exposures, 20.0 +/- 5.7 vs 21.6 +/- 4.7), but these differences were not significant (p = NS). Patients developed an intense tan significantly earlier with 5-MOP than with 8-MOP (3.5 +/- 0.5 weeks vs 4.4 +/- 0.5 weeks; p < 0.01). CONCLUSION Bath-5-MOP-UVA was more phototoxic than bath-8-MOP-UVA. It was more effective in the treatment of palmar psoriasis, whereas its greater pigmentogenic activity appeared to have an adverse effect on therapeutic effectiveness in the treatment of plaque-type psoriasis.

Merkel-cell carcinoma in Behçet's disease.

Sir, Merkel-cell carcinoma (MCC) is a rare malignant tumour of the skin which is highly aggressive; frequent recurrences and distant spread are common (1). Behçet’s disease (BD) is a multisystem vasculitis, with oral and genital aphthous ulcers, cutaneous vasculitis, uveitis and arthritis as its main features (2). Association of BD with malignant tumours, mainly solid neoplasms, has been described, but a review of the literature showed no report of an association between BD and cutaneous tumours. We herein report the case of a patient affected with BD who subsequently developed a MCC.

‘Activation-induced cell death’: a special program able to preserve the homeostasis of the skin?

Abstract: The ‘activation‐induced cell death’ (AICD) is a molecular system leading to death of antigen‐activated T lymphocytes, in order to avoid accumulation of harmful cytokine‐releasing cells. This article reviews both the molecular mechanisms working in AICD and the role played by such mechanisms in preventing a number of skin diseases. Specifically, because AICD removes activated and autoreactive T cells through a CD95‐/CD95‐L‐mediated suicide, skin diseases were scrutinized in which such valuable machinery could be lacking. Indeed, at least some inflammatory skin diseases, including psoriasis and atopic dermatitis, can be sustained by an increased survival of activated T lymphocytes associated with deficient CD95‐/CD95‐L‐mediated AICD of such strong pro‐inflammatory cells. In addition, autoreactive skin diseases, including, e.g. alopecia areata, lichen planus and other lichenoid tissue reactions, can be related to autoreactive T lymphocytes which could be unable to undergo CD95‐/CD95‐L‐mediated AICD. Finally, a lack of AICD may be executive even in favoring cutaneous T cell lymphoma. Thus, because inflammatory, autoreactive and neoplastic skin diseases can be associated with a deficient CD95‐/CD95‐L‐mediated suicide of activated T cells, AICD is likely to represent a fundamental program to preserve the homeostasis of the skin. Therapeutic approaches able to restore the AICD machinery promise to successfully treat such relevant skin diseases.

Identification of Fas-L-Expressing Apoptotic T Lymphocytes in Normal Human Peripheral Blood: In Vivo Suicide

Fas-L molecules expressed by in vitro stimulated T cells may be critically involved in suicidal activation-induced cell death (AICD) of such cells through engagement of their Fas receptors. A similar suicide of T cells was postulated to occur even in vivo, to eliminate dangerous activated lymphocytes; however, the demonstration of suicidal AICD of T cells in healthy humans in vivo is still lacking. We therefore investigated the possible occurrence of Fas-L-linked suicidal apoptosis of T cells in normal human peripheral blood. For this purpose, we took advantage of immunoelectron microscopy, which allows simultaneous visualization of the morphological apoptotic cellular changes together with surface expression of Fas-L molecules. Very few T lymphocytes were observed showing the ultrastructural features of apoptotic lymphocytes; these occasional apoptotic T cells, together with the majority of the normal T cell population, expressed the Fas molecule on the plasma membrane, as expected. Interestingly, the apoptotic cells were also Fas-L-positive, whereas normal T cells were Fas-L-negative. Such Fas-L-associated T cell suicide operating in vivo in healthy individuals is presumably able to suppress immune responses and prevent autoreactivity, thus maintaining the homeostasis of human blood.

Specific skin infiltration as first sign of chronic myelomonocytic leukemia with an unusual phenotype

A patient who had a plaque on his forehead as the first sign of chronic myelomonocytic leukemia (CMML) is described. Histologic studies, which formerly led to the misdiagnosis of non-Hodgkins lymphoma, revealed CMML with an unusual phenotype. This represents a rare type of CMML for the following reasons: (1) specific cutaneous involvement is rarely the first sign of CMML; (2) the unique phenotype was detected by immunohistology on lesional skin, specifically, the leukemic infiltrate was CD4-positive and notably negative for CD15, the pan myeloid/monocytic marker.