Autoimmune bullous diseases in non-HIV Kaposi's sarcoma: a retrospective study in a large cohort of patients.

BACKGROUND: Kaposi's sarcoma (KS) is a rare endothelial neoplasm caused by the human herpesvirus 8 (HHV-8). Its risk is increased in immunocompromised patients, including those undergoing immunosuppressive therapy for autoimmune bullous diseases. Conversely, HHV-8 infection has been hypothesized to be a triggering factor of bullous diseases, especially pemphigus. Given the fact that both KS and autoimmune bullous diseases have a low incidence in the general population, it could be expected that the association between these disorders would be exceptional. OBJECTIVES: To assess the frequency of bullous diseases in a large cohort of non-HIV KS patients and to describe our experience concerning the clinical features, natural history and treatment options in this setting. METHODS: We performed a retrospective review of all patients with non-HIV KS in association with bullous disease followed at our department between 1990 and 2016. Medical records were reviewed for demographics, medical history, clinical characteristics and treatment. RESULTS: Among 1362 patients with classic or iatrogenic KS, 14 (1.03%) also suffered from bullous disease. The mean age at diagnosis of both disorders was 85.8 years with a male/female ratio of 9 : 5. Among these 14 cases, nine (0.66%) were associated with bullous pemphigoid (BP), three (0.22%) with localized BP and two (0.15%) with pemphigus vulgaris. Seven had developed a bullous disease after being diagnosed with KS, while in the remaining seven cases, KS developed after the onset of bullous disease. As expected, KS worsened when corticosteroids were used. CONCLUSION: Bullous diseases seem to be more frequent among patients with KS, supporting the hypothesis that HHV-8 may be involved in their pathogenesis. Therapeutic management of these cases should take into account KS-inducing potential of corticosteroids.

Toe web intertrigo in Kaposi's sarcoma patients: a microbiological study in a large cohort of patients.

Kaposi 's sarcoma (KS) is a rare multifocal angioproliferative disease associated with human herpes virus 8 (HHV-8) infection, characterized by cutaneous nodules or plaques especially on the lower limbs. Some skin modifications, such as chronic lymphedema, plantar hyperkeratosis and interdigital desquamation, may be associated with consequent impairment of the local immunosurveillance and increased risk of some bacterial or mycotic infections. With the objective of evaluating if bacterial or mycotic infections in KS patients are supported by different microorganisms compared to control patients, we performed an observational retrospective study, comparing positive cultural swabs of interdigital intertrigo of KS patients with positive cultural swabs of interdigital intertrigo of patients admitted to our dermatologic unit during the last 10 years. One hundred KS patients and 84 control patients were admitted to this study. Some of the skin swabs from interdigital spaces were positive for more than one microorganism, and therefore we found 187 microorganisms among the KS group and 182 microorganisms in the control group. The most common microrganisms among KS patients were T. mentagrophytes (16%), S. aureus (14.9%), P. aeruginosa (13.9%), S. marcescens (5,9%), while among non-KS patients were S. aureus (26,9%), C. albicans (22%), S. agalactiae (7.7%) and E. coli (9.9%). These differences are statistically significant (p < 0.01). KS patients may be more affected by toe web intertrigo due to other bacteria and dermatophytes than the general population. During clinical examination, a careful inspection is necessary for an early diagnosis of toe web intertrigo, in order to prevent serious complications, such as cellulitis and sepsis. Consequently, a cultural examination with antibiogram is required to identify the causative agent of intertrigo and guide antimicrobial therapy.

Iatrogenic Kaposi's Sarcoma: a Retrospective Cohort Study in an Italian Tertiary Care Centre.

AIMS: Kaposi's sarcoma (KS) is a lymphoangioproliferative multicentric disorder. Among its four distinct clinical variants, iatrogenic KS (iKS) typically affects patients who have received immunosuppressant regimens for organ transplants, proliferative disorders, or immune-mediated diseases. The aim of the current study was to examine the characteristics of a cohort of patients with iKS, evaluating the differences in terms of epidemiological and clinical features, management and outcomes between organ transplant recipients (OTR) and patients immunosuppressed for other medical conditions. MATERIALS AND METHODS: This retrospective study included, out of 1389 KS patients, 143 patients suffering from iKS being followed in an Italian tertiary care centre from November 1995 to December 2016. Demographic data, clinical features, previous immunosuppressive therapies, management, and outcomes were recorded for each patient. RESULTS: We detected iKS in 10.3% of the analysed KS population. The mean age was 71.9 years in non-OTR versus 51.4 years in OTR (P = 0.04). Staging at diagnosis showed a more severe disease in non-OTR than in OTR, with stage IA observed in 33.3% of OTR versus 11.8% of non-OTR (P < 0.001) and stage IVB in 29.1% of non-OTR versus 12.1% of OTR (P = 0.001). Corticosteroids represented the most frequent immunosuppressive drugs at diagnosis in both groups, in conjunction with cyclosporine A in OTR. Immunosuppressant reduction or withdrawal was carried out in 93.9% of OTR versus 63.6% of non-OTR (P < 0.001). CONCLUSIONS: As corticosteroids and cyclosporine A are the most common iKS-inducing drugs, their reduction or withdrawal, wherever possible, is needed. Differences in disease severity at presentation between OTR and non-OTR may interfere with the choice of management strategy and the consequent outcome.

Detection of Polyomavirus in Merkel cell carcinoma by immunohistochemistry: report of three cases.

Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine carcinoma of the skin, arising from pluripotent precursors of Merkel cells. The tumor most frequently affects head and neck of elderly patients. It increases with sun exposure and after immunosuppression and organ transplantation. Because of a possible viral association, interest in MCC has escalated. A new polyomavirus, Merkel cell polyomavirus (MCPyV), was identified and associated to MCC. In support of this hypothesis, we report three new clinical cases of MCC in which we detected MCPyV by immunohistochemistry and provide an update on current thinking about the MCC.

Continuous exposure to Kaposi sarcoma-associated herpesvirus (KSHV) in healthcare workers does not result in KSHV infection.

Kaposi sarcoma (KS)-associated herpesvirus (KSHV or HHV-8) infection routes and risk of occupational exposure are still ill-defined. We analysed the risk for occupational acquisition of KSHV infection in healthcare workers (HCWs) with prolonged professional exposure to patients with classic KS, comparing the results to those obtained in healthy relatives of KS patients. Serum and/or saliva KSHV-specific antibodies and DNA were detected in five out of 35 healthy relatives of KS patients but in none of the eight HCWs, suggesting that, outside strict family contacts, horizontal transmission of KSHV is highly inefficient even for HCWs with prolonged contact with KS patients.

Intralesional vincristine as first-line therapy for nodular lesions in classic Kaposi sarcoma: a prospective study in 151 patients.

BACKGROUND: Classic Kaposi sarcoma is a rare angioproliferative neoplasm with varying biological behaviour. Depending on the clinical stage, local or systemic therapy can be used. Vincristine has proven to be effective as systemic chemotherapy and in very few reports as intralesional treatment. OBJECTIVES: Our aim was to determine the efficacy and safety of intralesional vincristine in the treatment of classic Kaposi sarcoma nodular lesions. METHODS: We conducted a prospective, open-label, single-centre clinical trial in 151 patients with stage IB classic Kaposi sarcoma. Vincristine was injected in a single nodule (0.3-0.8 mm) on the lower limb. Another similar lesion on the same limb, at a distance of >or= 10 cm, or on the contralateral limb, was kept under clinical observation as control. Adverse effects were evaluated after 1 week, and efficacy after 4 and 12 weeks. RESULTS: One hundred and fifty-one patients were enrolled. At final evaluation, 115 patients presented complete response (76.1%), 28 had partial response (18.5%), six had improvement (4%), one had stable disease (0.7%) and only one patient had tumour progression (0.7%). Therefore the total response rate was 98.7% (149 patients). Therapy was generally well tolerated. The most frequently registered adverse events, observed in 21 patients (13.9%), were erythema and itching. CONCLUSIONS: Intralesional vincristine is an effective and safe treatment for nodular lesions in classic Kaposi sarcoma and can be recommended as first-line therapy in initial stages and as support therapy in advanced stages.

Herpes simplex virus infection and pemphigus.

Pemphigus is a group of autoimmune blistering diseases of the skin and/or mucous membranes caused by the presence of antibodies against adhesion molecules on the cell surface of keratinocytes. In genetically predisposed patients, several factors, including drugs, physical agents, neoplasms, hormones, and viruses, notably herpes simplex virus (HSV), have been hypothesized to trigger or exacerbate the disorder. To clarify whether HSV infection represents an aetiopathogenetic factor for pemphigus or a consequence of the immunosuppressive treatment, skin and/or mucosal swabs from 35 patients with pemphigus vulgaris or pemphigus foliaceus were tested for HSV by polymerase chain reaction. Twenty-three of these patients were newly diagnosed, while the remaining 12 had had a previous diagnosis and were under treatment with low-dosage oral corticosteroids. Repeat swabs were taken two weeks after starting intensive immunosuppressive therapy in 8 HSV-negative patients. All skin swabs (n=27) resulted negative for both HSV-1/2, while oral swabs (n=30) were positive for HSV-1 in 5 out of the 12 patients who were being treated with oral corticosteroids, but in none (n=19) of the non-treated group (p=0.0067, X2 test). Five out of the 8 patients with repeat swabs became positive for HSV-1, prompting us to start antiviral therapy. In conclusion, HSV is unlikely to be a triggering factor for pemphigus, but its presence in pemphigus lesions seems to be a frequent and early complication of immunosuppression.

Widespread idiopathic pyoderma gangrenosum evolved from ulcerative to vegetative type: a 10-year history with a recent response to infliximab.

Pyoderma gangrenosum (PG) is an infrequent neutrophilic dermatosis, which commonly presents with a limited number of ulcerative, pustular, bullous or vegetative lesions associated with an underlying systemic disorder. We report a 34-year-old man with ulcerative PG that was exceptionally widespread and not associated with any other condition. Moreover, it was resistant to steroid treatment and, after prolonged use of ciclosporin, it unexpectedly developed a vegetative pattern, further supporting the hypothesis that the different forms of PG are part of a single clinical spectrum. Finally, dramatic improvement of the condition occurred after treatment with infliximab, an antitumour necrosis factor-alpha monoclonal antibody; however, this produced circulating autoantibodies. Although this has not had any clinical consequence to date, accurate follow-up in patients treated with infliximab is essential to monitor the onset of a possible autoimmune disorder induced by the drug.