Use of biologics for psoriasis in solid organ transplant recipients.

Biologics have significantly advanced the treatment of inflammatory disorders, including psoriasis. However, their use in immunosuppressed patients, such as those with solid-organ transplants, is less understood. These patients often face dermatological issues, but inflammatory skin diseases are rare due to their immunosuppressive treatments. Our study aims to assess biologics' effectiveness in such immunocompromised patients. We report a case from our institution of a 29-year-old man with a history of psoriasis, who underwent a kidney transplant and later developed erythroderma. He did not respond to traditional treatments and was successfully treated with adalimumab, leading to the discontinuation of MMF. We also reviewed literature in solid organ transplant patients with psoriasis. Our findings, based on 10 articles, indicate a cautious approach to using biologics in this group, with further research needed for efficacy and safety.

The Pro-Differentiation Effect of Doxycycline on Human SZ95 Sebocytes.

BACKGROUND: Despite their widespread clinical use in both acne vulgaris and rosacea, the effects of tetracyclines on sebocytes have not been investigated until now. Sebaceous glands are central to the pathogenesis of acne and may be important in the development of rosacea. OBJECTIVE: The aim of this study was to assess the effects of doxycycline on the immortalized SZ95 sebaceous gland cell line as a model for understanding possible effectiveness on the sebaceous glands in vivo. METHODS: The effects of doxycycline on SZ95 sebocyte numbers, viability, and lipid content as well as its effects on the mRNA levels of peroxisome proliferator-activated receptors α and γ, in comparison to the peroxisome proliferator-activated receptor γ agonist troglitazone, were investigated. RESULTS: Doxycycline reduced the cell number and increased the lipid content of SZ95 sebocytes in vitro after 2 days of treatment. These doxycycline effects may be explained by an upregulation of peroxisome proliferator-activated receptor γ mRNA levels at 12 and 24 h, whereas troglitazone already upregulated peroxisome proliferator-activated receptor γ levels after 6 h. Both compounds did not influence peroxisome proliferator-activated receptor α mRNA levels. CONCLUSION: These new findings illustrate a previously unknown effect of doxycycline on sebocytes, which may be relevant to their modulation of disorders of the pilosebaceous unit, such as acne vulgaris and rosacea.

The impact of switching to mTOR inhibitor-based immunosuppression on long-term non-melanoma skin cancer incidence and renal function in kidney and liver transplant recipients.

Background: Solid organ transplantation is associated with increased risk of non-melanoma skin cancer. Studies with short follow up times have suggested a reduced occurrence of these cancers in recipients treated with mammalian target of rapamycin inhibitors as maintenance immunosuppression. We aimed to describe the occurrence of skin cancers in renal and liver transplant recipients switched from calcineurin inhibitor to sirolimus-based regimes.Methods: We performed a retrospective study of sirolimus conversion within the Irish national kidney and liver transplant programs. These data were linked with the National Cancer Registry Ireland to determine the incidence of NMSC among these recipients. The incidence rate ratio (IRR) for post versus pre-conversion NMSC rates are referred in this study as an effect size with [95% confidence interval].Results: Of 4,536 kidney transplants and 574 liver transplants functioning on the 1 January 1994 or transplanted between 1 January 1994 and 01 January 1994 and 01 January 2015, 85 kidney and 88 liver transplant recipients were transitioned to sirolimus-based immunosuppression. In renal transplants, the rate of NMSC was 131 per 1000 patient years pre-switch to sirolimus, and 68 per 1000 patient years post switch, with adjusted effect size of 0.48 [0.31 - 0.74] (p = .001) following the switch. For liver transplant recipients, the rate of NMSC was 64 per 1,000 patient years pre-switch and 30 per 1,000 patient years post switch, with an adjusted effect size of 0.49 [0.22 - 1.09] (p .081). Kidney transplant recipients were followed up for a median 3.4 years. Liver transplants were followed for a median 6.6 years.Conclusions: In this study, the conversion of maintenance immunosuppression from calcineurin inhibitors to mTOR inhibitors for clinical indications did appear to reduce the incidence of NMSC in kidney and liver transplant recipients.

Post-transplant malignancy in solid organ transplant recipients in Ireland, The Irish Transplant Cancer Group.

OBJECTIVE: Solid organ transplant recipients are at increased risk of cancer compared to the general population. To date, this risk in Ireland has not been investigated. We conducted a national registry study of cancer incidence following solid organ transplantation. METHODS: National centers for solid organ transplantation supplied their respective registry databases to cross-reference with episodes of malignancy from the National Cancer Registry Ireland (NCRI) between 1994 and 2014. Standardized incidence of cancer post-transplant was compared to the general population by means of standardized incidence ratios (SIRs), and between solid organ transplant types by incidence rate ratios. RESULTS: A total of 3346 solid organ transplant recipients were included in this study. Kidney transplant recipients constituted the majority of participants (71.2%), followed by liver (16.8%), heart (6.4%), and lung (5.6%) transplants. The most common cancers within the composite of all transplant recipients included the following (SIR [95% CI]): squamous and basal cell carcinoma (20.05 [17.97, 22.31] and 7.16 [6.43, 7.96], respectively), non-Hodgkin lymphoma (6.23 [4.26, 8.59]), and renal cell carcinoma (3.36 [1.96, 5.38]). CONCLUSIONS: This study reports the incidence of cancer following solid organ transplantation in Ireland. These results have significant national policy implications for surveillance, and early diagnosis in this patient group.

Variation in Nonmelanoma Skin Cancer Incidence by Treatment Modality Among Patients Receiving Multiple Kidney Transplants.

IMPORTANCE: Existing data suggest that nonmelanoma skin cancer (NMSC) is more common in renal transplant recipients than in maintenance dialysis patients. However, whether the risk of NMSC varies as the treatment modality for end-stage kidney disease (ESKD) changes between dialysis and transplantation is not well described. OBJECTIVE: To determine whether the incidence of NMSC is attenuated during periods of graft loss with a return to dialysis in those who receive multiple kidney transplants. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of data from recipients of kidney transplants from the Irish National Kidney Transplant Service database, linked with the Irish Cancer Registry, from 1994 to 2014. All analysis took place between January 10, 2018 and March 31, 2018. Standardized incidence ratios (SIRs) were calculated for NMSC incidence in comparison with the general population using Irish census data as the denominator. Incidence of NMSC was calculated with modality of treatment for ESKD varying over time; incidence rates and rate ratios associated with dialysis intervals were calculated using Poisson regression; and disease was defined according to International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for cancer diagnosis. EXPOSURES: Kidney transplantation. MAIN OUTCOMES AND MEASURES: Incidence rates per 1000 patient-years and incident rate ratios of NMSC after kidney transplant. RESULTS: Data from the records of 3821 deceased or living donor kidney transplant recipients were assessed; 2399 (62.8%) male and 1422 (37.2%) female recipients; mean (SD) age at time of first data recorded, 41.9 (16.0) years. A total of 3433 recipients were included who had a functioning transplant on January 1, 1994, or received a transplant after that date up to December 31, 2014: 3215 received 1 transplant, 522 a second kidney transplant, and 84 had 3 or more kidney transplants. Periods of treatment with a functioning transplant were associated with a higher incidence of NMSC diagnosis than periods of graft failure: adjusted incidence rate ratio (aIRR), 2.19 (95% CI, 1.56-3.07), P < .001. The aIRRs of NMSC fell from 41.7 (95% CI, 39.38-44.15) per 1000 patient-years in the first transplant to 19.29 (95% CI, 13.41-27.76) in the dialysis period following the first allograft failure. Incidence similarly rose and fell following each subsequent consecutive transplant. CONCLUSIONS AND RELEVANCE: In recipients of multiple kidney transplants, while the incidence of NMSC fell during periods defined by transplant failure, there was residual elevated risk. While ascertainment bias may have contributed to the observed trends, the stagnant incidence of invasive cancer overall highlights the need for continued cancer surveillance during graft failure.