A fifth subtype of Kaposi's sarcoma, classic Kaposi's sarcoma in men who have sex with men: a cohort study in Paris.

BACKGROUND: Classic Kaposi's sarcoma (CKS) occurs predominantly among elderly men and is associated with Kaposi's sarcoma-associated herpesvirus (KSHV). In low-endemic countries, KSHV infects predominantly men having sex with men (MSM). OBJECTIVES: To describe a cohort of classic Kaposi sarcoma in a low-endemic area for KSHV, to highlight the features of CKS in MSM and identify prognostic factors. METHODS: Retrospective single-centre study of CKS cases. We compared MSM to heterosexual patients. Then, we divided the patients into two subgroups, those requiring a systemic treatment and the others, and we performed univariate and multivariate analyses to determine aggressiveness of CKS. RESULTS: Between 2006 and 2015, seventy-four patients were included. Mean age at diagnosis was 68.9 years; sex ratio (M/F) was 6.4, and 28% were MSM; MSM patients were younger (P = 0.02), less often originated from endemic areas (P < 0.0001). KS was less severe (P = 0.04), required more often a local treatment than a systemic one (P = 0.03). On multivariate analysis, CD4 T-cell count > 500/mm3 at baseline was associated with a reduced risk of severe evolution. CONCLUSION: First CKS cohort in low-endemic zone. We describe a fifth subtype of KS: KS in MSM. The CD4 T-cell count was found to correlate with prognosis.

Vemurafenib pharmacokinetics and its correlation with efficacy and safety in outpatients with advanced BRAF-mutated melanoma.

Vemurafenib is a BRAF kinase inhibitor approved for first-line treatment of metastatic BRAF (V600) -mutant melanoma. However, data on the pharmacokinetic/pharmacodynamic (PK/PD) relationship are lacking. The aim of this prospective, multicenter study was to explore the PK/PD relationship for vemurafenib in outpatients with advanced BRAF-mutated melanoma. Fifty-nine patients treated with single-agent vemurafenib were prospectively analyzed. Vemurafenib plasma concentration (n = 159) was measured at days 15, 30, 60, and 90 after treatment initiation. Clinical and biological determinants (including plasma vemurafenib concentration) for efficacy and safety were assessed using Cox's model and multivariate stepwise logistic regression. Median progression-free survival (PFS) and overall survival were 5.0 (95 % confidence interval [95 % CI] 2.0-6.0) and 11.0 (95% CI 7.0-16.0) months, respectively. Twenty-nine patients (49 %) experienced any grade ≥3 toxicity and the most frequent grade ≥2 toxicity was skin rash (37 %). Severe toxicities led to definitive discontinuation in seven patients (12 %). Grade ≥2 skin rash was not statistically associated with better objective response at day 60 (p = 0.06) and longer PFS (hazard ratio 0.47; 95 % CI 0.21-1.08; p = 0.075). Grade ≥2 skin rash was statistically increased in patients with ECOG ≥ 1 (odds ratio 4.67; 95 % CI 1.39-15.70; p = 0.012). Vemurafenib concentration below 40.4 mg/L at day 15 was significantly associated with a shorter PFS (1.5 [0.5-5.5] vs. 4.5 [2-undetermined] months, p = 0.029). Finally, vemurafenib concentration was significantly greater in patients developing grade ≥2 rash (61.7 ± 25.0 vs. 36.3 ± 17.9 mg/L, p < 0.0001). These results suggest that early plasma drug monitoring may help identify outpatients at high risk of non-response or grade ≥ 2 skin rash.

Late occurrence of Histoplasma duboisii cutaneous and pulmonary infection 18 years after exposure.

We report an imported case of Histoplasma capsulatum var. duboisii (H. duboisii) infection in a white French woman revealed by cutaneous lesions of the scalp, 18 years after her last stay in West and Central Africa. Asymptomatic bilateral pulmonary infiltrates were discovered on thoracic computed tomography. Skin biopsy allowed the positive diagnosis showing the typical yeasts; culture of biopsy specimens was positive for H. capsulatum. In the absence of criteria of severity, the patient was treated for one year with oral itraconazole 400mg/day. The outcome was favourable, skin and pulmonary lesions resolved slowly. The follow up is 5 years without relapse after the end of treatment. This case illustrates the possibility of late occurrence of H. duboisii infection, many years after exposure and the major importance of asking any patient for travelling or residency in tropical countries.

Acute kidney injury in patients with severe rash on vemurafenib treatment for metastatic melanomas.

Vemurafenib, a selective BRAF (v-raf murine sarcoma viral oncogene homologue B1) kinase inhibitor, is a new targeted biotherapy that improves survival in patients with metastatic melanomas harbouring the BRAF V600E mutation. However, this drug has significant dermatological adverse effects. We report a new severe cutaneous reaction to this drug associated with acute kidney injury (AKI). Four patients presented a generalized grade 3 (Common Terminology Criteria for Adverse Events) erythematous eruption with hyperkeratosis pilaris, 5-14 days after the introduction of vemurafenib. These symptoms were associated with AKI in all cases and transitory hypereosinophilia in two cases. Vemurafenib treatment was stopped in three patients and the dose was reduced in the fourth, leading to a gradual improvement of skin symptoms and renal function. Positron-emission tomography scans showed a complete response in three cases and a major response in one case. Vemurafenib was reintroduced at a lower dose, without a relapse of the rash, but renal function again deteriorated. Thus, we report a cluster of four cases of AKI associated with similar, severe, grade 3 cutaneous drug reactions related to vemurafenib.

Factors associated with severe skin infections in patients treated with biologic therapies for inflammatory rheumatic diseases.

BACKGROUND: The incidence of severe infections is increased under biologic therapies and the skin is the second localization. OBJECTIVE: To appraise the factors associated with severe skin infections (SSI) in patients under biologic therapies for inflammatory rheumatic diseases (IRD). METHODS: We performed a case-control (ratio 1:3) study nested in a prospective cohort of patients with IRD. SSI was defined as requiring hospitalization or intravenous anti-infectious therapy. We defined two imbedded periods: period A was the time window between the first biologic therapy and the SSI; period B was the last 3 or 12 months (for tumor necrosis factor blockers or rituximab, respectively) before the SSI. RESULTS: Among 4,361 patients with IRD, 29 had a SSI under biologic therapy. In multivariate analyses, SSI were significantly associated with smoking, baseline C-reactive protein and gammaglobulinemia, non-steroidal anti-inflammatory drugs before biologic therapy, cumulative dose of steroids, concomitant steroids during period A, number of different biologic therapies during period A, treatment with infliximab during period A, period B or as first biologic therapy and treatment at high dose during period B. CONCLUSION: In patients under biologic therapies for IRD, the risk of SSI is associated with several factors including tobacco, treatment with infliximab or high dose range.

[Primary effusion lymphoma in two kidney transplant recipients]. / Lymphome des séreuses chez le transplanté rénal: deux cas.

BACKGROUND: Primary effusion lymphoma (PEL) is a highly malignant non-Hodgkin lymphoma associated with Kaposi's sarcoma-associated herpesvirus/human herpesvirus-8 infection (KSHV/HHV-8). It is chiefly seen in HIV patients and is rare in transplant recipients, possibly going unrecognized. OBSERVATION: We describe two male kidney transplant recipients, aged 47 and 51 years, followed for Kaposi's sarcoma in skin, lymph nodes, gastrointestinal (GI) tract and lung whose disease was poorly controlled by sirolimus and chemotherapy. Recurrent pleural effusion contrasted with reduction of cutaneous Kaposi lesions. KHSV viral loads were negative or very low in plasma, were negative or very low, whereas those in pleural effusion were high. Lymphoma cells were discovered only seven to nine months after the initial effusion despite repeated needle biopsies. In one patient, tumour cells were co-infected with Epstein-Barr virus. CONCLUSION: The contrast between a very low KHSV viral load in plasma and a very high viral load pleural effusion should alert physicians and prompt suspicion of PEL in Kaposi's sarcoma patients with recurrent serous effusion. The potential inhibitory role of sirolimus on PEL progression is discussed.