Melanoma in solid organ transplant recipients.

This manuscript outlines estimated risk and clinical course of pretransplant MM, donor-transmitted MM and de novo MM posttransplantation and includes an analysis of risk factors for metastasis, data from clinical studies and current and proposed management. MM in situ and thin melanoma (<1 mm) in the transplant population has similar recurrence and survival estimates to those in the general population. A minimum wait time of 2 years prior to transplantation is suggested for MM with a Breslow depth <1 mm and no clinical evidence of metastasis. More advanced MM may adopt a more aggressive course in transplant recipients. Sentinel lymph node biopsy may be of additional prognostic benefit. Revision of immunosuppression in the management of de novo melanoma in collaboration with the transplant team should be considered. Larger studies utilizing uniform staging criteria or at minimum Breslow depth, are required to assess true risk and outcome of MM in the immunosuppressed transplant population. Emphasis remains on patient education and regular screening to provide early detection of MM.

Phaeohyphomycosis due to Alternaria species in transplant recipients.

Alternaria species are members of a heterogeneous group of dematiaceous fungi that rarely cause opportunistic infections in transplant recipients. During a 20-year period from 1989 to 2008, 8 solid organ transplant recipients (63% males; median age, 48 years) developed Alternaria species infections at the Mayo Clinic. All patients were highly immunocompromised as evidenced by their receipt of multiple transplants, treatment of acute and chronic allograft rejection, and occurrence of other opportunistic infections. All patients presented with non-tender erythematous or violaceous skin papules, nodules, or pustules in exposed areas of the extremities. No case of visceral dissemination was observed. Itraconazole was the most common drug used for treatment, although voriconazole, posaconazole, and caspofungin could potentially be useful based on our limited clinical data and in vitro antifungal susceptibility testing. One patient was treated with voriconazole, while another patient who was refractory to itraconazole had rapid resolution of lesions after the addition of caspofungin. Attempts at antifungal therapy alone were unsuccessful; all patients eventually required surgical excision of lesions. In conclusion, Alternaria species are rare but increasingly recognized opportunistic infections among highly immunocompromised transplant recipients. Wide excisional surgery combined with prolonged systemic antifungal therapy and reduction in immunosuppressive regimens provided the best chance of cure. Although itraconazole remains the most common drug for treatment, this case series highlights the potential clinical utility of caspofungin, voriconazole, and posaconazole as alternative regimens.

Mycobacterium marinum infections in transplant recipients: case report and review of the literature.

Infections due to Mycobacterium marinum are rarely encountered following organ and tissue transplantation. Herein, we report a case of M. marinum infection in a kidney and pancreas transplant recipient who manifested clinically with multiple locally spreading sporotrichoid-like cutaneous nodules in his left forearm. In order to provide a general overview of post-transplant M. marinum infections, we reviewed and summarized all previously reported cases of this infection that occurred after transplantation. Including our index case, all 6 cases presented with multiple cutaneous and subcutaneous nodules that had spread locally in the involved extremity. One patient had lesions located in non-contiguous body sites suggesting either systemic dissemination or multiple sites of inoculation. In all but 1 patient, the cutaneous nodules appeared in an ascending pattern and following exposure to fish tanks or after contact with the marine environment. The diagnosis of M. marinum infection was suspected on clinical grounds and confirmed by mycobacterial culture. Treatment consisted of at least 2 active antibiotics (such as rifamycins, ethambutol, tetracyclines, or macrolides) for 4-9 months, resulting in clinical cure or improvement. Relapse was observed in 1 patient despite completing 6 months of antibiotic therapy. One patient had surgical excision of the lesions. In conclusion, M. marinum should be considered as the cause of cutaneous and subcutaneous nodules in transplant recipients, particularly in the context of fish tank or marine exposure. Compared with the immunocompetent hosts, M. marinum infection may have a more aggressive clinical course after transplantation, and may require a longer duration of antibiotic treatment. Early diagnosis and treatment may prevent local spread and potential systemic dissemination.

Reduction of immunosuppression for transplant-associated skin cancer: thresholds and risks.

BACKGROUND: Although evidence supports the efficacy of reducing immunosuppression for transplant-associated skin cancer, clinical thresholds for and risks associated with reduction are not well defined. OBJECTIVES: In this study, experienced transplant physicians were surveyed regarding appropriate thresholds for consideration of reduction of immunosuppression and the likelihood of rejection and allograft compromise associated with various levels of reduction. PATIENTS AND METHODS: Fifty-two transplant physicians reviewed 13 hypothetical patient scenarios with graduated morbidity and mortality risk and provided opinions on the degree of reduction of immunosuppression that was warranted and the risks associated with various degrees of reduction. RESULTS: Renal, liver and cardiac transplant physicians generally concurred on the level of reduction of immunosuppression warranted by various degrees of skin cancer. As morbidity and mortality from skin cancer increased, physicians were more likely to accept risk to allograft function from more aggressive reduction. CONCLUSIONS: Reduction of immunosuppression is considered a reasonable adjuvant strategy in recipients of solid organ transplants who have substantial morbidity and mortality risk from skin cancer. Physicians are willing to accept an increased risk of allograft compromise when confronted by severe or extensive skin cancer. Further research is needed to define the precise correlation among levels of reduction of immunosuppression, therapeutic efficacy, and concomitant risks.

Oral retinoids for chemoprevention of skin cancers in organ transplant recipients: results of a survey.

Systemic retinoid therapy is thought to be beneficial for chemosuppression of skin cancers in solid organ transplant recipients. We present the results of a survey of 28 dermatologists with experience managing transplant recipients to clarify when and how systemic retinoids are used in this population. Almost 80% of respondents use retinoids in some transplant recipients. Factors influencing the use of retinoids include the incidence and aggressiveness of cutaneous squamous cell carcinomas and the extent of concomitant actinic keratoses. Patients are monitored more closely during periods of dose adjustment than during the maintenance phase of therapy. Adverse effects are variably managed symptomatically, with dose adjustment, by discontinuation of retinoids, or by referral to another specialist for further evaluation. In the absence of large randomized controlled trials, the practice habits of experienced physicians serve as a useful guide for the use of oral retinoids in transplant recipients.

Reduction of immunosuppression for transplant-associated skin cancer: expert consensus survey.

BACKGROUND: Reduction of immunosuppression is considered a reasonable adjuvant therapeutic strategy in solid-organ transplant recipients experiencing multiple or high-risk skin cancers. However, the literature provides no guidance about what threshold of cancer development would warrant initiation of reduction of immunosuppression. OBJECTIVES: To develop expert consensus guidelines for initiation of reduction of transplant-associated immunosuppression for solid-organ transplant recipients with severe skin cancer. METHODS: An expert consensus panel was convened by the International Transplant Skin Cancer Collaborative and Skin Care for Organ Transplant Patients Europe Reduction of Immunosuppression Task Force. Thirteen hypothetical patient scenarios with graduated morbidity and mortality risks were presented and mean and mode expert opinions about appropriate level of reduction of systemic immunosuppression (mild, moderate, severe) were generated. RESULTS: Mild reduction of transplant-associated immunosuppression was considered warranted once multiple skin cancers per year developed or with individual high-risk skin cancers. Moderate reduction was considered appropriate when patients experienced > 25 skin cancers per year or for skin cancers with a 10% 3-year risk of mortality. Severe reduction was considered warranted only for life-threatening skin cancers. CONCLUSIONS: Reduction of immunosuppression is considered a reasonable adjuvant management strategy for transplant recipients with numerous or life-threatening skin cancers. Proposed guidelines are presented for the graduated reduction of immunosuppression coincident with the increasing skin cancer risks.

Anxiolysis with oral midazolam in pediatric patients undergoing dermatologic surgical procedures.

BACKGROUND: Pediatric patients undergoing dermatologic surgical procedures often experience high levels of anxiety. Oral midazolam is a short-acting benzodiazepine that can ameliorate procedure-related anxiety. OBJECTIVE: Our purpose was to determine the safety and efficacy of oral midazolam as an adjuvant anxiolytic agent for pediatric patients undergoing dermatologic surgical procedures. METHODS: A prospective series of pediatric patients undergoing dermatologic surgical procedures who received oral midazolam were monitored, and efficacy and complications were recorded. RESULTS: Oral midazolam provided good to excellent anxiolytic effects in most pediatric patients undergoing painful dermatologic surgical procedures. Because midazolam does not provide analgesic effects, local anesthesia is necessary. Complications were uncommon and minor. CONCLUSION: Oral midazolam is an effective anxiolytic agent in pediatric patients undergoing dermatologic surgical procedures.

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.

Rhinophyma and coexisting occult skin cancers.

BACKGROUND: Although coexistent tumors have been reported in patients with rhinophyma, few reports have described the coexistence of rhinophyma and an occult infiltrating squamous cell carcinoma (SCC). OBJECTIVE: Preoperatively and during rhinophymaplasty, recognition of subtle changes can suggest an underlying malignancy. METHODS: A large infiltrating SCC was noted during electrosurgical rhinophymaplasty. Mohs micrographic surgery was performed to clear the tumor. RESULTS: The patient was tumor-free with no evidence of recurrence at 1-year follow-up. CONCLUSION: In the evaluation of changing rhinophyma or subtle changes in tissue noted during rhinophymaplasty, physicians must consider the possibility of an underlying malignancy.

The management of melanoma and nonmelanoma skin cancer: a review for the primary care physician.

In the United States, the incidence of skin cancer is greater than that of all other cancers combined, and early diagnosis can be lifesaving. A substantial public health concern, skin cancer is increasingly being diagnosed and managed by primary care physicians. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) (known collectively as nonmelanoma skin cancer) and malignant melanoma are the most common cutaneous malignancies. Shave biopsy is usually performed if BCC is suspected; punch biopsy is preferred if SCC is thought to be present. The choice of biopsy techniques depends on the presumed depth of the lesion. Treatment has 3 goals: complete eradication of the cancer and preservation or restoration of normal function and cosmesis. Risk of recurrence or metastasis determines whether the tumor is high risk or low risk. Based on the level of risk, treatment options are considered, including whether the patient can be treated by a primary care physician or should be referred to a dermatologist. Choice of treatment approach depends on the tumor's location, size, borders, and growth rate. The standard treatment approaches are superficial ablative techniques (electro-desiccation and curettage and cryotherapy) used primarily for low-risk tumors and full-thickness techniques (Mohs micrographic surgery, excisional surgery, and radiotherapy) used to treat high-risk tumors. Removal of the entire tumor is essential to limit and prevent tumor recurrence.

Safe and effective conscious sedation administered by dermatologic surgeons.

OBJECTIVE: To review the experience with conscious sedation administered by dermatologic surgeons at an academic medical center. DESIGN: Retrospective medical chart review. SETTING: Outpatient dermatologic surgery unit at an academic medical center. PATIENTS: Fifty episodes of conscious sedation in 37 patients undergoing dermatologic surgical procedures. INTERVENTION: Intravenous and inhaled conscious sedation was administered with strict monitoring during procedures. MAIN OUTCOME MEASURES: Efficacy was subjectively recorded by the administering physician and complications were recorded. RESULTS: Administration of conscious sedation by dermatologic surgeons was associated with good to excellent sedation with minimal complications. Extensive preparation and training were necessary, and strict guidelines devised by a conscious sedation task force were followed. Emergency preparedness was high, although it was not used. CONCLUSIONS: Conscious sedation can be safely and effectively administered by dermatologic surgeons in a hospital-based outpatient surgical unit after extensive training. Emergency preparedness is essential, and conservative guidelines should be followed.

Conscious sedation of pediatric patients with combination oral benzodiazepines and inhaled nitrous oxide.

BACKGROUND: Pediatric patients undergoing surgical procedures may experience considerable anxiety. Use of conscious sedation may be helpful in managing mild to moderate anxiety. OBJECTIVE: To assess the effectiveness of combination oral benzodiazepines and inhaled nitrous oxide conscious sedation in pediatric surgical patients. METHODS: Eleven episodes of conscious sedation in eight pediatric patients were prospectively monitored, with recording of indications, patient characteristics, clinical scenarios, surgical procedure, sedative regimen, quality of sedation, and complications. Extensive training in conscious sedation had been obtained, and emergency preparedness was at a high level. RESULTS: Combination oral benzodiazepines and inhaled nitrous oxide produced good to excellent results in all patients but one. Complications were uncommon and mild. No emergency intervention was necessary. CONCLUSION: Monitored use of a combination of oral benzodiazepine and low to moderate concentrations of inhaled nitrous oxide can provide safe and effective conscious sedation in pediatric patients. Training in conscious sedation and emergency preparedness are essential.

Alar batten cartilage grafting in nasal reconstruction: functional and cosmetic results.

BACKGROUND: Alar batten cartilage grafts can restore form and function to a compromised ala, prevent stenosis of the nasal valve, and maintain unrestricted air movement. Soft tissue reconstructive options can be combined with alar batten grafts. OBJECTIVE: Our purpose was to analyze functional and cosmetic outcomes in a series of patients undergoing alar batten cartilage grafting. METHODS: We analyzed the functional and cosmetic outcomes of 25 patients in whom reconstruction involved alar batten cartilage grafts. Assessment included defect characteristics, function and cosmesis (rated by physician and patient), and complications. RESULTS: Eighty-three percent of patients had good to excellent functional and cosmetic results by patient and physician assessment. Three patients were rated as having poor cosmetic results by the physician; all 3 patients graded these results as good. One episode of graft failure occurred, and recipient and donor site complications were minor. CONCLUSION: Alar batten cartilage grafts appear to be an excellent option for reconstruction of substantial alar defects.

Infiltrating basal cell carcinoma in the setting of a venous ulcer.

A 77-year-old man was referred with a 5-year history of an intermittently painful, nonhealing right medial ankle ulcer. The ulcer had not responded to multiple treatment modalities, including Unna boots, compression therapy, sclerotherapy, and split-thickness skin grafting. The past medical history was significant for a deep venous thrombosis in the right leg 30 years earlier (treated with warfarin for 3 months) and a history of greater saphenous vein harvesting for coronary bypass grafting 28 years previously. After the vein stripping, the patient had suffered from increasing right leg edema and stasis changes in the right leg. His history was also remarkable for coronary artery disease, dyslipidemia, and lymphoma treated with chemotherapy 8 years before presentation, with no evidence of recurrence. He had stopped smoking approximately 20 years earlier. Medications included atenolol, simvastatin, nicardipine, nitroglycerin, and aspirin. Skin examination revealed a 3.0 x 3.5-cm ulcer adjacent to the medial malleolus. The edges of the ulcer appeared raised and rolled (Fig. 1). Centrally, there was granulation tissue, which appeared healthy. There were surrounding dermatitic changes. Dorsalis pedis and the posterior tibial pulses were normal. Noninvasive vascular studies revealed severe venous incompetence of the right popliteal and superficial veins. Arterial studies and transcutaneous oximetry were normal. Computed tomographic scan of the pelvis did not reveal any adenopathy, and radiographic imaging did not reveal any bony changes suggestive of osteomyelitis. Biopsy of the ulcer edge and base showed infiltrating basal cell carcinoma (Fig. 2). Mohs' micrographic surgery required three layers; the final extent of the ulcer was 7.8 x 6.9 cm. A split-thickness skin graft was placed.

Treatment of facial wounds with botulinum toxin A improves cosmetic outcome in primates.

Surgeons have constantly sought to achieve the most aesthetic scar. A major factor determining the final cosmetic appearance of a cutaneous scar is the tension acting on the wound edges during the healing phase. Since Theodor Kocher pioneered the alignment of skin incisions with Langer's lines in 1892, surgical techniques that attempt to overcome closing tension have become standard. Yet, no treatment has been available to minimize underlying muscle contractions, which are the major cause of this tension. Botulinum toxin A is a potent drug that produces temporary muscular paralysis when injected locally. It has proven to be safe and effective in the treatment of a variety of disorders, including hyperkinetic facial lines. The objective of this randomized, double-blind, placebo-controlled primate study was to investigate the efficacy of a single injection of botulinum toxin A to improve the cosmetic appearance of cutaneous scars. Symmetric pairs of standardized excisions were performed on either side of the forehead of six primates. The half foreheads were randomized to the botulinum toxin A treatment side versus the placebo injection side. A panel of three blinded facial surgeons assessed the cosmetic appearance of the mature scars 3 months postoperatively. The wounds that had been immobilized with botulinum toxin A were rated as significantly better in appearance than the control wounds (p < 0.01). Histologic examination confirmed that all scars were mature. Blinded, randomized, placebo-controlled human clinical trials are presently under way at the Mayo Clinic.