Skin diseases in Turkish renal transplant recipients

BACKGROUND: Organ transplant recipients are predisposed to a variety of cutaneous complications due to immunosuppressive therapy. We aimed to determine the prevalence and the clinical spectrum of skin diseases in renal transplant recipients (RTRs). METHODS: One hundred and eleven RTRs were examined at the Renal Transplantation Center in Ege University Hospital between October 1999 and October 2001. The effects of age, gender and duration time after transplantation on cutaneous manifestations were evaluated and the dermatologic manifestations in RTRs were compared with findings in a control group consisting of 100 patients. The t-test, chi2 test and Fisher's exact test were used for statistical analysis. RESULTS: Seventy-five patients (66.4%) had an infection of the skin, 66 patients (58.4%) had drug-related manifestations, and 11 patients (9.7%) had premalignant or malignant skin lesions. Human papilloma virus (HPV) infections were the most common skin lesions. There was no significant relation between age and gender and the incidence of skin diseases in RTRs. The incidence of HPV infections, tinea versicolor and premalignant and malignant lesions increased with the duration of immunosuppression. The incidence of infectious skin diseases, especially HPV infections and tinea versicolor, was higher in the study group than in the control group. CONCLUSIONS: In this study, we observed that cutaneous lesions, especially those caused by infectious diseases, had a higher frequency in RTRs. The findings emphasize the importance of regular dermatological screening in these patients, which can provide early diagnosis and a better quality of life for RTRs.     

The impact of skin disease following renal transplantation on quality of life

BACKGROUND: The immunosuppressive therapy a patient requires to sustain a functioning renal allograft in the long term is associated with various skin complications. While quality of life (QoL) after renal transplantation has been studied, no publications document the effect of post-transplant dermatological complications on QoL. OBJECTIVES: The objective of the study was to document the prevalence of the skin diseases that commonly occur in association with post-transplant immunosuppression. A general dermatological quality of life questionnaire, the Dermatology Life Quality Index (DLQI), was used to assess the QoL effect of these cutaneous complications. The study was designed to examine further the impact of age, sex, duration since transplant and immunosuppressive regimen on the DLQI score of renal transplant recipients (RTR). METHODS: One hundred and seventy-three RTR completed the DLQI, were interviewed and examined for evidence of common post-transplant skin diseases. RESULTS: Sixteen per cent of RTR had DLQI scores >6, reflecting a significant impact on their QoL. Dry skin, itch, hypertrichosis, sebaceous gland hyperplasia, acne, genital warts and a history of >4 herpes simplex virus type 1 infections in the past year were all found to have a significant impact on the quality of life (P < 0.05). Multivariate analysis revealed that the greatest impact on QoL was in RTR who were younger, female and with multiple skin problems (P < 0.05). CONCLUSIONS: The dermatological complications of immunosuppressive therapy are common in RTR and can significantly impair QoL in certain individuals. Visible, infectious and cosmetic skin problems had most impact on QoL while a history of skin cancer had a lesser impact. Early dermatological referral and careful choice of immunosuppression may enhance the QoL, particularly in young and female RTR.     

Skin lesions in adult liver transplant recipients: a study of 100 consecutive patients

BACKGROUND: The surgical advances made in the area of organ transplantation along with the use of more efficacious immunosuppression have meant an increase in patient survival. This longer-living transplant population has started to exhibit cutaneous problems, some of which lead to an increased mortality while others lead to a decline in the quality of life. OBJECTIVES: The primary objective was to determine the different types of cutaneous lesions encountered in the adult liver transplant population. Secondary objectives were to determine the impact, if any, of the duration of transplant, the type of immunosuppression involved and the degree of sun exposure and skin phototype, on the skin cancers encountered in this transplanted population. METHODS: Two dermatologists examined 100 consecutive liver transplant recipients (LTRs) attending the transplant outpatient department. Skin examination included the face and whole body and lesions found were categorized into the following groups: cutaneous malignancies, squamoproliferative lesions, cutaneous infections and others that did not fall into any of these categories. RESULTS: The reasons for organ transplantation were numerous. The mean age at transplantation was 42.5 years. The average time since transplantation was 5.5 (range 0.75-16 years). Four patients developed skin cancers; among them there were a total of seven skin cancers (one squamous cell carcinoma, six basal cell carcinomas). Fungal infections accounted for 19% of all cutaneous infections seen, viral infections 2% and bacterial infections 5%. Triple-drug immunosuppressive therapy (ciclosporin A, azathioprine and prednisolone) was used in 35% of LTR patients, while dual therapy (tacrolimus and prednisolone) was used in 48% and monotherapy (tacrolimus) was used in 17% of LTRs. CONCLUSIONS: Immunosuppressive therapy is believed to be one of the most important risk factors in the development of skin cancer in solid organ transplant recipients. The relatively low prevalence of skin cancer in our liver transplant population may in part be explained by the relatively high percentage of recipients on dual and monotherapy (48% and 17% respectively), and the shorter duration of therapy. Our study suggests that although LTRs are at higher risk of developing nonmelanoma skin cancer than the general population, the risk is comparable with other solid organ transplant recipients.     

Risk factors for cutaneous wart onset in transplant recipients

INTRODUCTION: Transplant recipients are at increased risk for cutaneous warts. We have investigated the delay of their onset warts and some possible risk factors for their occurrence. PATIENTS AND METHODS: Clinical data were summarized on a standard question and examination sheet. Warts were diagnosed on clinical grounds and course duration assessed on patients' report. Immunosuppressive therapy and HLA group were collected from clinical transplantation records. An actuarial curve was used to evaluate the delay of onset of warts. To compare associated risk factors among the two groups (patients with warts and patients without warts) at 1 year and 3 years following transplant, single variate analysis was performed. RESULTS: At the time of transplant, the prevalence of warts was 16 p. 100. It was increased with the duration of immunosuppression: 23 p. 100 at 1 year, 35 p. 100 at 3 years, 45 p. 100 at 5 years and 54 p. 100 at 7 years. Warts were multiple and principally localized on the hands. Transplant recipients without cutaneous warts 3 years after transplant had less intensive immunosuppressive therapy than the group with cutaneous warts. No association was found between age, sex, HLA markers, actinic keratosis and wart onset. DISCUSSION: The prevalence of warts increases with the duration of transplantation. Cutaneous warts are generally multiple and have a chronical course without spontaneous remission. More intensive immunosuppressive therapy increases their occurrence. This trial cannot evaluate the association between carcinoma and warts. On the basis of our study, there is no relationship between actinic keratosis and warts, nor HLA markers and warts.     

Prevalence of benign cutaneous disease among Oxford renal transplant recipients

Background The burden of malignant and benign cutaneous disease among renal transplant recipients (RTR) is substantial. Little attention is given to non‐malignant skin problems in the literature despite their potential impact on quality of life or on aesthetics – which may contribute to poor compliance with immunosuppressive medications post‐transplantation. Objectives The aim of this study was to examine prevalence of benign cutaneous disease in a group of RTRs and identify risk factors for individual cutaneous conditions. Methods All cutaneous findings were recorded in a single full body skin examination of 308 RTRs. Data on medical, transplant and medication history were obtained from questionnaire and medical records. Odds ratios were calculated to look at associations between benign cutaneous diseases and various potential risk factors after controlling for gender, age, time since transplantation and skin type. Results Cutaneous infections such as viral warts (38%), fungal infection (18%) and folliculitis (27%) were common and usually chronic. A range of pilosebaceous unit disorders were observed with hypertrichosis being strongly associated with ciclosporin (P < 0.0001). Other iatrogenic cutaneous effects included gingival hyperplasia (27%) and purpura (41%). We identified seborrhoeic warts and skin tags in 55% and 33% respectively. Inflammatory dermatoses were rare (< 2%) apart from seborrhoeic dermatitis (9.5%). Discussion In this first comprehensive study on prevalence of benign cutaneous diseases in a UK transplant population, a wide range of skin disorders was identified. It is therefore important that RTRs have access to dermatology services post‐transplantation for appropriate management of benign cutaneous conditions as well as early detection of cutaneous malignancy and education regarding risks of sun exposure.     

Decreased skin cancer after cessation of therapy with transplant-associated immunosuppressants

BACKGROUND: Immunosuppression for solid organ transplantation is associated with increased incidence of internal and cutaneous malignant tumors, among which skin cancer is the most common. OBJECTIVE: To determine the effects on cutaneous carcinogenesis when stopping therapy with immunosuppressive medications. OBSERVATIONS: We followed the clinical course of 6 solid organ transplant recipients after therapy with immunosuppressant medications was stopped because of allograft failure or unacceptable cutaneous carcinogenesis. Generally, we found that stopping therapy with immunosuppressive medications resulted in deceleration of cutaneous carcinogenesis, resolution of cutaneous verrucae vulgaris, and qualitative improvements in skin condition. Four patients experienced marked improvement; 2 did not. CONCLUSIONS: Cessation of transplant-associated therapy with immunosuppressive medications for patients in whom cutaneous carcinomas developed after transplantation may lead to deceleration of cutaneous carcinogenesis, decreased verrucae, and improved skin quality within 1 to 2 years. Because of the natural variation in skin cancer development and the small number of cases in this series, definitive conclusions require further study.     

Optimal Management of Skin Cancer in Immunosuppressed Patients

Skin cancer is the most common malignancy in humans with basal cell carcinoma representing the majority of cases in the general population. The prevalence of skin cancer is increased amongst immunosuppressed patients such as those with lymphoproliferative disorders including non-Hodgkin lymphoma and chronic lymphocytic leukemia or those with iatrogenic immunosuppression following organ transplantation. In addition, these patients experience greater morbidity and mortality associated with skin cancers. The most common skin cancer in immunosuppressed patients is squamous cell carcinoma, which often presents with more aggressive features and has a greater rate of metastasis. This article reviews the risk factors, etiology, clinical presentation, and prevalence of skin cancer amongst immunosuppressed patients, including organ transplant, lymphoproliferative disorders, autoimmune disorders, and human immunodeficiency virus. We also provide a comprehensive review of treatment guidelines for immunosuppressed patients with cutaneous malignancy. Surgical therapy is the cornerstone of treatment; however, we also discuss pharmacologic treatment options, lifestyle modifications, and revision of immunosuppressive regimens.     

Skin cancer and other cutaneous disorders in liver transplant recipients

Patients who have received liver transplant are at increased risk of skin complications due to long-term immunosuppression regimen. The aim of this study was to analyze the incidence and risk factors of skin complications in liver transplant patients. We analyzed 161 liver transplant recipients. The mean age at transplantation was 47.4 years. Mean follow-up was 6 years. Seventy-one percent of patients presented with skin complications, including aestethic alterations, infections, precancerous lesions and malignancies, which represented 57%, 43%, 18% and 9%, respectively. Risk factors were: age at transplantation ≥ 45 years, immunosuppressive therapy with cyclosporine, and phototype II and III. Our study indicates that although liver transplant recipients are at greater risk of developing skin complications compared to the general population, the risk is lower than for other solid organ transplants, particularly for premalignant and malignant lesions.     

Cutaneous squamous cell carcinomas and papillomaviruses in renal transplant recipients: a clinical and molecular biological study.

Papillomaviruses are strongly implicated in squamous cell carcinomas arising on mucosal surfaces of normal individuals, and in the skin carcinomas of epidermodysplasia verruciformis suffers. Renal transplant recipients often have numerous skin warts and, in Australia particularly, a very high risk of developing cutaneous squamous cell carcinoma. To determine the magnitude of this risk, and to test whether papillomaviruses are specifically associated with these cancers, we examined 188 renal transplant recipients for skin cancers and tested 235 biopsy specimens of (histologically proven) squamous cell carcinomas for the presence of viral DNA. The risk of developing squamous cell carcinoma increased with duration of transplant: the probability being 25% after 9.5 years (standard error = 1.3 years) rising to 50% at 20.6 years (standard error 6.8 years). Factors which did not appear to affect the risk of tumour development included the patients sex and their skin type. However the age at transplant significantly altered the risk with patients transplanted at greater than 35 years developing tumours about four times more rapidly than patients less than or equal to 35 years. Extensive hybridisation tests for the presence of papillomavirus DNA in squamous cell carcinomas were negative, as was the polymerase chain reaction amplification method using general L1 gene oligonucleotide primers. Our data do not support a role for papillomavirus in the maintenance of cutaneous squamous cell carcinoma.     

A prospective study of the incidence of skin cancer and its risk factors in a Spanish Mediterranean population of kidney transplant recipients

BACKGROUND: Skin cancer is the most common malignancy occurring in kidney transplant recipients (KTRs). OBJECTIVES: Our purpose was to investigate, prospectively, the cumulative incidence of cancerous and precancerous skin lesions as well as their risk factors in a close follow-up population of KTRs from a Mediterranean area of Spain. PATIENTS AND METHODS: One hundred and seventy-four consecutive KTRs were examined at the moment of transplant and then at 6-month intervals. The cumulative incidence of skin cancer was computed. To analyse the role of potential risk factors (age at transplantation, cause of renal failure, duration of pretransplant dialysis, type of immunosuppressive regimen, sun-reactive skin type and history of occupational sun exposure), the Cox regression method was used. RESULTS: After a median follow-up of 72 months (range, 12-140), 39 patients (25.3%) developed 142 tumours [84 basal cell carcinoma (BCC) and 58 squamous cell carcinoma (SCC)]. The BCC/SCC ratio was 1.4 : 1. The cumulative incidence for skin cancer was 13% after 3 years of graft survival, increasing to 27.5% at 6 years and 48% at 10 years. Only age at the time of transplantation and occupational sun exposure had statistical significance as risk factors (P < 0.001). CONCLUSIONS: Our study confirms the high incidence of non-melanoma skin cancer among KTRs in a Mediterranean population with occupational sun exposure and the patient's age at the time of transplantation being the main risk factors. We believe that all organ transplant programs should provide educational information about protecting oneself from the sun as well as include follow-up visits by dermatologists in order to facilitate early diagnosis and treatment of skin cancer.     

Skin cancer in organ transplant recipients: Epidemiology,pathogenesis, and management

In the United States more than 100,000 people are living with solid organ transplants. The intense immunosuppressive regimens necessary for prolonged survival of allografts significantly increase the rates of both internal and cutaneous malignancies in recipients of solid organ transplants. Skin cancer is the most common cancer in patients after transplantation. Because of the early onset and high tumor burden in transplant recipients, dermatologists have significant challenges in managing the treatment of these patients. This article describes the epidemiology and clinical presentation of skin cancer during posttransplantation immunosuppression, discusses pathogenic cofactors, and reviews the optimal management for mild and severe skin cancer in transplant recipients.     

Skin lesions in renal transplant patients after 10-23 years of immunosuppressive therapy

Ninety-eight patients with 10-23 years of uninterrupted immunosuppressive therapy due to renal transplants were investigated for signs of skin disease. Thirty-seven per cent had or had had premalignant or malignant skin lesions. This is significantly different from a control population (p less than 0.0001). There was also a correlation between the length of the immunosuppressive therapy and the risk of acquiring squamous cell skin cancers (p less than 0.05). Fifty-five per cent had common viral warts at the time of the present examination. The duration of immunosuppressive therapy also correlated with the presence of warts (p less than 0.01). Seven patients had mycosis and four patients had seborrheic eczema. In one-third of the patients the skin appeared normal.     

THE SKIN AND IMMUNOSUPPRESSION*

Of 135 kidney allograft recipients twenty one (15.5%) developed a total of 84 malignant skin tumours from 4 to 115 months after transplantation. Seven of these patients also developed a total of 12 keratoacanthomas. Skin lesions due to viral, fungal and opportunistic organisms were prevalent but serious pyogenic skin infections were not increased. In contrast, of 50 patients on immunosuppressive therapy for glomerulonephritis or collagen diseases, only two had skin tumours; none of which were squamous cell carcinomas.     

BENIGN AND MALIGNANT SKIN LESIONS IN RENAL TRANSPLANT RECIPIENTS

Background:

Skin lesions – benign and malignant – occur frequently in organ transplant recipients receiving long-term immunosuppressive therapy. These patients are at greater risk of skin cancers.

Aims:

To study dermatologic problems in renal transplant recipients (RTRs).

Methods:

One hundred patients (53 men and 47 women) were consecutively examined for benign and malignant skin complications since transplantation in Razi Hospital in Tehran Medical University. The main immunosuppressive therapy regimen in these patients was a combination of prednisolone, azathioprine, and cyclosporine.

Results:

The early and most common complication was cosmetic side effects that occurred in 98% patients. Skin infections occurred in 83% of the patients and most of them were viral infections (65%), especially of human papilloma viruses (HPVs) in 40% of the patients. We found six cases of malignancy in these patients in that four cases were skin cancers, including one case of SCC, one BCC, and two cases of Kaposi''s sarcoma. Dermatologic problems occur most frequently in RTRs, especially skin cancers which have higher frequency in these patients than general population, particularly, Kaposi sarcoma. Sun exposure has an important role in developing epithelial skin cancers following transplantation. The age of developing skin cancer in these patients was early than normal population.

Conclusion:

Our results emphasize the importance of dermatologic examinations and monitoring RTRs to obtain an early diagnosis and treatment of cutaneous manifestations.     

Calcineurin activity and inhibition in skin and (epi)dermal cell cultures

Calcineurin (Cn) is the target of the immunosuppressive drugs cyclosporine A (CsA), tacrolimus (Trl), and pimecrolimus (Prl). Trl and Prl are often used topically for treatment of various skin diseases. The Cn inhibitors CsA and Trl are mostly used for maintenance therapy of transplant patients. Their long-term use, however, causes a dramatic increase in skin cancer risk. By using a newly developed assay for Cn measurement in blood, we were able to demonstrate Cn activity in total skin homogenates. A significantly higher activity was found in epidermis compared to dermis. In skin cell cultures, fibroblasts showed the highest activity as compared to keratinocytes and melanocytes. Of the Cn inhibitors, Trl showed stronger inhibition than CsA and Prl (57 and 55% in fibroblast and keratinocyte cultures, respectively). Also, the lowest IC(50) (the half maximal inhibitory concentration) values were found for Trl (0.5 and 1.3 nM in two different fibroblast cultures). Cn activity and its inhibition can thus be studied in dermatological samples. The effects of Cn inhibition in fibroblasts and keratinocytes may be of influence on the overall functioning of the skin immune system.     

Mycosis fungoides after solid-organ transplantation: report of 2 new cases

Long-term survival after solid-organ transplantation is increasing because of recent advances, including new immunosuppressive regimens to avoid graft rejection. However, the resultant modification of the immune system is associated with an increased risk of several cancers. The most common are skin cancers, and lymphomas are second in frequency. Nevertheless, posttransplant primary cutaneous lymphomas (PCLs) are rare, and their incidence is not well known currently. From the files of the Nephrology and Cardiology Departments of University Hospital "12 de Octubre" of Madrid, we obtained clinical data from 1612 transplanted patients and only found 2 cases of posttransplant PCLs, both were T-cell PCL. We reviewed the clinical, histopathological, and immunohistochemical characteristics; both cases were T-cell posttransplant PCLs manifested clinically as mycosis fungoides. One was a 57-year-old woman who had received a cadaveric kidney transplant, and the other was a 60-year-old man with a heart transplant. Histology and immunohistochemistry were consistent with the features of mycosis fungoides when lesions were completely developed. Up to 20% of all organ transplant recipients will suffer some form of malignancy. Unlike general population, 70% of PCLs in transplant recipients are B cell in origin and frequently show positivity for Epstein-Barr virus markers; whereas only 30% are cutaneous T-cell lymphomas. Different pathogenic hypothesis including reduced immune surveillance, chronic antigenic stimulation by transplant grafts, and the direct oncogenic effects of immunosuppressive drugs have been suggested. Although cutaneous B-cell lymphomas are more common, dermatopathologists should be aware that cutaneous T-cell lymphomas may also appear.     

Melanoma in organ transplant patients

OBJECTIVE: The incidence of cutaneous melanoma has rapidly increased in the white population over the last decades. It has been estimated that the incidence doubles world-wide every 10 years. Different risk factors have been identified, including immunosuppression. The aim of our study-was to determine the relative risk of developing melanoma in the organ transplant population and the clinical and histological features of their melanomas. PATIENTS AND METHODS: This retrospective study was conducted with the collaboration of 9 University Hospital Centers: Besan?on, Brest, Caen, Dijon, Lille, Lyon, Nantes, Paris (Pitié-Salpétrière) and Rennes. A questionnaire was sent to the different departments of dermatology of these hospitals to obtain information on patients who had presented a melanoma after a transplantation between 1971 and 1997. During this period, there were 12,477 organ transplant recipients in the transplantation units of these 9 hospitals. Average follow-up for these patients was about 5 years and the average duration of immunosuppressive therapy was about 4.5 years. RESULTS: Among 12,477 organ transplant recipients, we found 17 cases of melanoma but no data could be obtain on one case: 14 occurred in renal transplant recipients and 3 in cardiac transplant recipients. Clinical and histological data were only available in 16 patients. The average time between transplantation and diagnosis of melanoma was 63 months, but it was 5 times shorter for 2 patients who had a past history of melanoma before transplantation. Two patients had a mucosal melanoma; for the cutaneous melanomas, 2 appeared on Dubreuilh melanosis, 2 were in situ melanomas, 7 were superficial spreading melanomas and 3 were nodular melanomas. The histological review of 11 cutaneous melanomas revealed a precursor nevus in 6 cases and a weak or no stroma reaction in 7/7 cases. Complete excision of the melanoma was performed in all patients except one with anorectal melanoma. Four patients died of visceral metastasis within a mean 15 months. The other 12 patients are still alive with a mean 3 year course since tumor treatment. We tried to determine the relative risk of developing melanoma in the renal transplant population (14 cases). The number of expected cases of melanoma was 5.54, giving a relative risk of 2.5. DISCUSSION: Only 4 studies have shown an increase in the incidence of melanoma in the renal transplant population: approximately 2 to 5-fold. In our study, the 2.5-fold increase in melanoma was estimated with an average 5 year follow-up and an average 5 year immunosuppressive therapy. This is probably an underestimation of risk because we were unable to make an exhaustive collection of cases of melanomas even though transplant recipients undergo more physical examinations than a reference population. The mean latency period from transplantation to melanoma diagnosis was 63 months, as in other studies. Histological examination showed that a precursor nevus is frequent with weak host cellular response to the tumor. The prognosis of these melanomas remains difficult to predict, but in our study, it would not appear to be as poor as expected. Discontinuation of immunosuppressive therapy would not appear to be necessary except in the presence of metastasis. Finally, our study demonstrates the importance of good patient follow-up, even after graft rejection due to the persistent risk of melanoma.     

Kaposi's sarcoma associated with immunosuppression for bullous pemphigoid

Kaposi's sarcoma may occur in transplant recipients on immunosuppressive regimens, but is not well recognized in association with treatment for dermatological disease. We report two cases where multifocal Kaposi's sarcoma developed following iatrogenic immunosuppression with prednisolone and azathioprine for bullous pemphigoid. Both patients were HIV negative and, in one case, lesions regressed both clinically and histologically when immunosuppressive therapy was withdrawn.     

Mortality and clinicopathological features of cutaneous squamous cell carcinoma in organ transplant recipients: a study of the Swedish cohort

Solid organ transplant recipients have a high incidence of cutaneous squamous cell carcinoma and often develop multiple and aggressive tumours. This retrospective study based on the Swedish organ transplant cohort, focuses on the deaths caused by cutaneous squamous cell carcinoma and aims to elucidate the clinicopathological features of these tumours. The cohort comprised 5931 patients who underwent organ transplantation during the period 1970 to 1997 and were registered in the Swedish In-patient Registry, Cancer Registry and Causes-of-Death Registry. A total of 544 cutaneous squamous cell carcinomas in 201 patients were re-examined. The dominating size of the tumours was 5-10 mm and one-third of the tumours were removed by methods other than excision surgery. Well-differentiated tumours and Clark level IV were predominant. Seven patients died from their tumours, all of which were localized on the head. The principal site of metastasis was the parotid gland. The mean duration between date of transplantation and death was 10.4 years (range 6-17 years). Mortality from cutaneous cell carcinoma was compared with that of the general population. There was a highly increased risk; standardized mortality ratio 52.2; 95% confidence interval 21.0-107.6. However, the mortality rate in the Swedish cohort appears to be lower than what has been reported previously from other countries.