Basal-Cell Carcinoma With Matrical Differentiation: Report of a New Case in a Renal-Transplant Recipient and Literature Review.

Basal-cell carcinoma with matrical differentiation (BCC-MD) is one of the rarest pathologic variants of basal-cell carcinoma, of which 41 cases have been so far reported in detail. One of them developed in a heart-transplant recipient. We report a new case of BCC-MD occurring in a renal-transplant recipient and review the relevant literature. A 75-year-old white man who had received a renal allograft 7 years ago developed a tumor on the left temple clinically suggestive of basal-cell carcinoma. Microscopically, the tumor associated features typical of basal-cell carcinoma (basaloid lobules with peripheral palisading and clefting) and pilomatricoma (presence of shadow/ghost cells). The 2 tumor components expressed variably beta-catenin, HEA/Ber-EP4, CD10, PHLDA-1, MIB-1/Ki67, calretinin, and bcl-2. BCC-MD has no distinctive clinical features. It affects predominantly male patients with a mean age of 69 years. More than half of cases appear on the head/neck area. Some cases harbor CTNNB1 mutations. Differential diagnosis includes tumors with matrical differentiation, namely pilomatrix carcinoma. The outcome is usually favorable after surgical excision, although regional lymph node metastases developed in 2 patients.

Profiling sirolimus-induced inflammatory syndrome: a prospective tricentric observational study.

BACKGROUND: The use of the immunosuppressant sirolimus in kidney transplantation has been made problematic by the frequent occurrence of various side effects, including paradoxical inflammatory manifestations, the pathophysiology of which has remained elusive. METHODS: 30 kidney transplant recipients that required a switch from calcineurin inhibitor to sirolimus-based immunosuppression, were prospectively followed for 3 months. Inflammatory symptoms were quantified by the patients using visual analogue scales and serum samples were collected before, 15, 30, and 90 days after the switch. RESULTS: 66% of patients reported at least 1 inflammatory symptom, cutaneo-mucosal manifestations being the most frequent. Inflammatory symptoms were characterized by their lability and stochastic nature, each patient exhibiting a unique clinical presentation. The biochemical profile was more uniform with a drop of hemoglobin and a concomitant rise of inflammatory acute phase proteins, which peaked in the serum 1 month after the switch. Analyzing the impact of sirolimus introduction on cytokine microenvironment, we observed an increase of IL6 and TNFα without compensation of the negative feedback loops dependent on IL10 and soluble TNF receptors. IL6 and TNFα changes correlated with the intensity of biochemical and clinical inflammatory manifestations in a linear regression model. CONCLUSIONS: Sirolimus triggers a destabilization of the inflammatory cytokine balance in transplanted patients that promotes a paradoxical inflammatory response with mild stochastic clinical symptoms in the weeks following drug introduction. This pathophysiologic mechanism unifies the various individual inflammatory side effects recurrently reported with sirolimus suggesting that they should be considered as a single syndromic entity.

Effect of two injections of non-adjuvanted influenza A H1N1pdm2009 vaccine in renal transplant recipients: INSERM C09-32 TRANSFLUVAC trial.

BACKGROUND: Enhancing vaccine immunogenicity in kidney transplant recipients, particularly against influenza, is required since the immunosuppression used to prevent graft rejection limits vaccine immunogenicity. We therefore investigated the immunogenicity and safety of a double dose non-adjuvanted vaccination regimen against influenza H1N1pdm2009 in kidney transplant adult recipients. METHODS: A prospective single-arm study was conducted including 121 renal transplant recipients under triple immunosuppressive regimen. Patients received 2 injections (day 0, day 21) of an inactivated, non-adjuvanted H1N1pdm2009 vaccine. Immunogenicity (hemagglutination-inhibition [HI] antibodies and anti-hemagglutin [HA] specific T cells) was evaluated after one and two injections (day 21, day 42) and at 6 months (day 182). RESULTS: The seroprotection rate (HI antibody titer≥1/40) was 19% at day 0 (n=119), 53% at day 21 (n=118), 60% at day 42 (n=116) (p=0.013; day 42 vs. day 21) and 56% at day 182 (n=113). The seroconversion rate was 24% and 32%, the geometric mean fold rise was 3.7 and 4.6 after the first and second injections, respectively. T-cell immunity to the H1N1pdm2009 vaccine showed a two-fold increase from baseline, though not statistically significant, in H1N1pdm2009-HA-specific CD4+ and CD8+ T cells in 34% and 48% of cases, respectively. No rejection episodes related to vaccination were observed while the donor-specific antibodies and creatinine clearance remained unchanged throughout the study. CONCLUSION: Administration of two doses of the non-adjuvanted influenza H1N1pdm2009 vaccine in renal transplant patients is safe and induces a significant seroprotection, not strong enough yet to meet European or US requirements for adults below 60 years, but comparable to seroprotection levels usually observed in the non immunosuppressed elderly population or conferred by a single dose of adjuvanted vaccine in solid organ transplant recipients. These results provide useful indications for future strategies required to improve immunogenicity of vaccines against influenza in transplanted patients.

Reversible ileitis secondary to high dose intravenous immunoglobulin in adult kidney transplant patient treated for acute humoral rejection.

Use of high dose intravenous immunoglobulin (IVIg) has been associated with necrotizing enterocolitis in late-preterm and term infants treated for severe isoimmune hemolytic jaundice. We present the first adult case of reversible ileitis related to high dose IVIg that occurred during the treatment of acute humoral rejection in a kidney transplant recipient (original nephropathy: lupus). At the third of the 5 days of a 0.4 g/kg/day IVIg infusion, he had periumbilical pain and nausea. Non-iodine injected abdominal computed tomography (CT) demonstrated a major proximal ileitis that was absent 1 month earlier on a previous CT. After the fourth injection, IVIg therapy was discontinued. Clinical and radiological signs disappeared, respectively, 5 and 7 days after IVIg discontinuation. No other causes of ileitis were diagnosed (especially infectious, vascular, or lupus-related bowel disease causes). Usual abdominal pain and nausea during IVIg therapy may be related to sub-clinical ileitis and/or enteritis. As in newborn, such complication has to be diagnosed and IVIg infusion discontinued because of potential evolution to intestinal necrosis.

Confounding factors for early death in incident end-stage renal disease patients: Role of emergency dialysis start.

Hemodialysis (HD) has been associated with higher 1-year mortality than peritoneal dialysis (PD) after dialysis start. Confounding effects of late referral, emergency dialysis start, or start with central venous catheter on this association have never been studied concomitantly. Survival was studied among the 495 incident dialysed patients in our department from 1995 to 2006 and followed at least 1 year until December 31, 2007. Nested Cox models adjusted on patient characteristics explored factors associated with 1-year and ≥1-year mortality. Hemodialysis patients were 332 (67.1%), 104 (21.0%) were late referred (<6 months), 167 (33.7%) started dialysis in emergency, and 144 (29.1%) started with central venous catheter. When adjusted only on age, sex, and comorbidities, HD was associated with poor 1-year outcome: adjusted hazard ratio (aHR) for death in HD vs. PD was 1.77, P=0.02. In fully adjusted model, among first dialysis feature variables, only emergency dialysis start was significantly associated with 1-year mortality: aHR 1.53, P=0.02. Dialysis modality was not associated with 1-year mortality rates in this fully adjusted model: aHR in HD vs. PD became 1.03, P=0.91. In ≥1-year period, HD was associated with lower mortality than PD (aHR 0.61, P=0.004), whereas other first dialysis features were not associated with death. Other factors associated with death were age, type 2 diabetes, peripheral vascular disease, heart failure, and hepatic failure. Negative association between HD and 1-year survival on dialysis was explained by confounders. Emergency dialysis start was strongly associated with early mortality on dialysis. Its prevention may improve patient survival.

Immunogenicity and safety of intradermal influenza vaccination in renal transplant patients who were non-responders to conventional influenza vaccination.

Seasonal influenza epidemics are associated with high morbidity and mortality particularly in high-risk patients. Conventionally administered influenza vaccines show reduced efficacy in populations with weakened immune systems such as solid-organ transplant patients. This study assesses the safety and immunogenicity of an intradermally administered influenza vaccine in renal transplant patients previously identified as non-responders to a licensed trivalent inactivated influenza vaccine (TIV). Renal transplant patients with low or no hemagglutination inhibiting (HI) antibody response to an A influenza (H3N2) vaccine strain were enrolled in a descriptive phase II, open-label, randomized, multicentre trial: 31 received an investigational intradermal TIV, and 31 received a conventionally administered TIV. Both vaccines contained 15 µg hemagglutinin (HA) per strain. The 62 study subjects were selected from 201 renal transplant patients aged 18-60 years who had been vaccinated in the previous year with a conventionally administered TIV. Vaccination was safe and well tolerated by each administration route. The immunogenicity results of this descriptive study showed ID TIV vaccination to induce HI antibody responses that trended higher in renal transplant patients than conventionally administered TIV. Our results suggest that ID influenza vaccination may offer enhanced immunogenicity and protection in persons who do not respond well to conventional TIV. Further studies should be conducted in immunocompromised populations to validate the trends for higher efficacy of ID vs. conventional route of immunization against influenza.

Poor prognosis of heart transplant patients with end-stage renal failure.

BACKGROUND: Chronic kidney disease (CKD) and end-stage renal failure (ESRF) are major complications after a heart transplant. The aim of this study is to compare survival in heart transplant (HT) vs non-heart transplant (non-HT) patients starting dialysis. METHODS: Survival was studied among the 539 newly dialysed patients between 1 January 1995 and 31 December 2005 in our Department. All patients were prospectively followed from the date of first dialysis up to death or 31 December 2005. Multivariate survival analysis adjusted on baseline characteristics was performed with the Cox model. RESULTS: There were 21 HT patients and they were younger than non-HT patients at first dialysis: 58.6+/-11.6 vs 63.0+/-16.2 years (P=0.09). Calcineurin inhibitor nephrotoxicity was the main cause of ESRF in HT patients (47.6%). Crude 1, 3 and 5-year survival rates in HT and in non-HT patients were as follows: 76.2%, 57.1%, 28.6% and 79.1%, 58.7%, 46.7% (P=0.2). The adjusted hazard ratio of death in HT vs non-HT patients was 2.27 [1.33-3.87], P=0.003. Sudden death was the main cause of death in HT patients, in 33.3% vs 10.4% in non-HT patients (P=0.01). Five HT patients benefited from renal transplant. They were all alive at the end of the study period, while one patient among the 16 remaining on dialysis survived. CONCLUSION: HT patients with CKD who reached ESRF have a poor outcome after starting dialysis in comparison with other ESRF patients. Improvement in renal function management in the case of CKD is needed in these patients and non-nephrotoxic immunosuppressive regimens have to be evaluated. Renal transplant should be the ESRF treatment of choice in HT patients.

Subsequent skin cancers in kidney and heart transplant recipients after the first squamous cell carcinoma.

BACKGROUND: The increased incidence of skin cancers in transplant patients is well documented; however, few data exist on the risk of subsequent skin tumors in a given patient after the first skin cancer. The aim of this study was to compare the individual rate of subsequent skin cancers in kidney (KTR) and heart transplant recipients (HTR) after the first squamous cell carcinoma (SCC) and to assess risk factors for tumor multiplicity. METHODS: In all, 188 patients (121 KTR/67 HTR) were studied for up to 5 years. The cumulative number of SCC, basal cell carcinomas, Bowen's diseases, premalignant keratoses, and keratoacanthomas was recorded yearly after the first SCC. RESULTS: Overall, 71% of patients developed 757 new skin tumors. At 5 years, 100% of HTR and 88% of KTR had presented new tumors. However, the mean number of all tumors was significantly higher in KTR (3.4 vs. 2.0, 4.8 vs. 2.6, 6.6 vs. 2.9, 8.5 vs. 3.5, and 9.7 vs. 4.6 at 1, 2, 3, 4, and 5 years, respectively). Transplantation before 1984, multiple tumors at first consultation, eye and hair color, and skin type were predictive of multiple tumors. Early minimization of immunosuppression and of sun exposure tended to be associated with a reduced rate of all tumors and of SCC, respectively. CONCLUSIONS: Although the proportion of HTR developing new tumors is greater as compared with KTR, the mean number of tumors per patient is higher in KTR. This could be due to a longer immunosuppression in patients younger at transplantation.