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.

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.

DNA sequence analysis and restriction fragment length polymorphism (RFLP) typing of the HLA-DQw2 alleles associated with dermatitis herpetiformis.

Dermatitis herpetiformis (DH) is a blistering autoimmune skin disease associated with a 95-100% incidence of the HLA class II antigen HLA-DQw2. Although the precise role of this antigen in the pathogenesis of DH is unclear, one theory proposes that patients with DH possess a molecularly unique subtype of the HLA-DQw2 antigen that causes immune abnormalities eventuating in the clinical manifestations of DH. To test this hypothesis, we performed DNA sequence analysis on the highly polymorphic HLA-DQB1 and HLA-DQA1 loci of eight patients with dermatitis herpetiformis. All DQB1 alleles sequenced were identical to the previously described HLA-DQB*0201 allele from HLA-DQw2 normal subjects. In addition, DQA1 alleles sequenced were identical to those alleles previously associated with HLA-DQw2 (DQA*0201, DQA*0501). These data document that although HLA-DQw2 appears to be a necessary element in the pathogenesis of DH, the development of DH is not dependent on the presence of a unique HLA-DQw2 antigen. HLA-DQ allelic typing by restriction fragment length polymorphism analysis of PCR-amplified HLA-DQA1 and HLA-DQB1 fragments was also performed in ten patients with DH to determine the allelic distribution among both HLA-DR3 (eight patients) and non-DR3 (two patients) DH patients. At the HLA-DQ beta chain locus, all patients possessed the DQB1*0201 allele. At the HLA-DQ alpha chain locus, all HLA-DR3 patients and one non-DR3 patient displayed a pattern consistent with the DQA1*0501 allele, whereas one non-DR3 patient displayed a pattern consistent with the DQA1*0201 allele. These data document that patients with DH do not express a unique HLA-DQw2 heterodimer, that the HLA-DQw2 molecules present in patients with DH have no DNA sequence differences from those found in normal HLA-DQw2 subjects and therefore that susceptibility to DH is not due to a unique HLA-DQw2 molecule.

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.

Comprehensive treatment of the aging face--cutaneous and structural rejuvenation.

As people age, characteristic changes occur in the skin, the soft tissue envelope, and the bony skeleton of the face and result in the aging face syndrome. An understanding of the pertinent biomechanical and histologic changes is necessary for developing an appropriate treatment plan. The advent of many new techniques, including cosmetic exfoliation, laser skin resurfacing, open rhinoplasty, and endoscopic, multiplane plastic surgical procedures, has enhanced therapy for the aging face syndrome. Treatment protocols should be individualized for each patient's needs and desires. Several of these recent treatments for facial rejuvenation are reviewed herein.

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.

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.

Complications of cutaneous surgery in patients who are taking warfarin, aspirin, or nonsteroidal anti-inflammatory drugs.

BACKGROUND AND DESIGN: No controlled studies exist with regard to the risks of continuing therapy with warfarin sodium or platelet inhibitors or the benefits of briefly discontinuing therapy with these agents in patients who are undergoing cutaneous surgical procedures. Our objective was to determine the frequency of complications of cutaneous surgery in patients who were receiving warfarin or platelet inhibitors and to evaluate whether preoperative discontinuation reduces complications. A retrospective, controlled study was performed of complications of excisional and Mohs micrographic surgery in 653 patients who were being treated with warfarin or platelet inhibitors or with their medications being briefly withheld. RESULTS: Severe complications of cutaneous surgery in patients who are taking warfarin or platelet inhibitors are uncommon, occur in 1.6% of cases, and are not significantly increased compared with complications in control subjects. Furthermore, there was no statistically significant reduction in the rates of severe complications in patients who had their medications preoperatively held. CONCLUSION: Cutaneous surgery in patients who receive warfarin or platelet inhibitors is associated with a low risk of severe complications, not significantly reduced by brief preoperative discontinuation.

Isotretinoin treatment of human immunodeficiency virus-associated eosinophilic folliculitis. Results of an open, pilot trial.

BACKGROUND: Human immunodeficiency virus-associated eosinophilic folliculitis is a pruritic eruption seen in advanced infection with human immunodeficiency virus. The associated pruritus causes considerable morbidity and is poorly responsive to conventional therapy. We studied whether isotretinoin would prove efficacious in the treatment of human immunodeficiency virus-associated eosinophilic folliculitis. Seven patients with biopsy specimen-proved human immunodeficiency virus-associated eosinophilic folliculitis were treated with a mean of 7.7 weeks of isotretinoin therapy and their responses were monitored. OBSERVATIONS: All patients responded with complete symptomatologic and clinical remission within 1 to 4 weeks of isotretinoin therapy. Four (57%) of seven patients remained in complete remission after just one course of isotretinoin therapy, while three (43%) of seven patients experienced up to three brief relapses, all rapidly responsive to further isotretinoin therapy. Patients remained free of disease for up to 9 months after therapy. CONCLUSIONS: Isotretinoin appears to be a promising treatment for human immunodeficiency virus-associated eosinophilic folliculitis. A double-blind, placebo-controlled trial is indicated.

Reinnervation of flaps and grafts of the face.

BACKGROUND: The degree to which disruption of sensory innervation is affected by flaps and grafts on the face has not been explored. The decision to choose a flap or a graft for reconstruction may affect future sensation at the surgical site. OBJECTIVES: To characterize the clinical recovery of sensory innervation after facial reconstructive surgery with flaps and grafts and to offer clinical guidelines on the recovery of sensation in reconstructed sites involving flaps and grafts of the face. METHODS: Seventy patients who underwent Mohs surgery and subsequent repair by either a flap or a graft were evaluated at different postoperative intervals. Fifty patients underwent flap reconstruction and 20 patients underwent graft reconstruction. Three principal modes of sensation were objectively assessed: light touch, temperature, and pinprick. RESULTS: Median time of evaluation after surgery was 11 months. The most common locations tested were the nose (36 patients) and the forehead (9 patients). Postoperative evaluation showed that flap sensation recovery to light touch was present in 10% of patients before 3 months, 41% of patients from 3 to 12 months, 27% of patients from 1 to 2 years, and 75% of patients after 2 years. Graft sensation recovery to light touch was present in no patients evaluated less than 2 years after surgery and in 29% of patients evaluated more than 2 years after surgery. After adjustments for postoperative size and interval, patients with flaps were more likely than those with grafts to have touch sensation at the time of testing (adjusted odds ratio, 8.91; 95% confidence interval, 1.06-74.62; P = .04), to be able to distinguish between warm and cold (adjusted odds ratio, 3.99; 95% confidence interval, 1.05-15.16; P = .04), and to be able to distinguish between sharp and dull (adjusted odds ratio, 27.31; 95% confidence interval, 2.20-339.71; P = .01). CONCLUSIONS: Predictable factors are associated with sensation recovery in patients with flaps and grafts. The recovery of sensory innervation after surgery is earlier with flaps than with grafts. Our data provide clinicians with guidelines for recovery of sensation that ultimately will reassure the patient.

Factitious disease of periocular and facial skin.

PURPOSE: To describe the clinical appearance of factitious (or self-inflicted) lesions on periocular skin and face. METHODS: All patients with factitious cutaneous disease who were examined at Mayo Clinic, Rochester, Minnesota, between 1985 and 1997 were identified. For patients with lesions on the face and periocular skin, the demographic features, clinical descriptive characteristics of their lesions, associated psychopathology, and treatments were ascertained. RESULTS: Of 38 patients with factitious dermatitis, 18 (47%) had facial lesions. Of these 18 patients, 15 (83%) were female. The mean age (+/- SD) of the patients with facial lesions was 35.2 +/- 15.7 years (range, 9 to 66 years). Eight patients (44%) had neurotic excoriations, nine (50%) had dermatitis artefacta, and one (6%) had trichotillomania. The working diagnoses of five patients cared for initially in the Department of Ophthalmology were corneal epithelial and facial desquamation associated with severe pain of unknown cause, medial cicatricial ectropion of probable vasculitic cause, basal cell carcinoma of the nasojugal fold, recurrent preseptal cellulitis resistant to medical treatment, and madarosis of the upper eyelids of unknown cause. CONCLUSION: Cutaneous factitious disease may masquerade as numerous clinical entities and should be included in the differential diagnosis of lesions of the periocular skin.

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.

Medium-depth chemical peeling.

Trichloroacetic acid (TCA) alone or in combination with other agents is the mainstay of medium-depth chemical peels. Indications for medium-depth chemical peels include both medical conditions, such as diffuse photodamage with contiguous actinic keratoses, and cosmetic conditions, such as the aging face and solar lentiginosis. Medium-depth chemical peeling with TCA is relatively simple and is associated with a favorable risk/benefit ratio. However, proper patient selection, with attention to both medical and psychological factors, requires significant experience. The histological basis of the rejuvenating effects of TCA peels is well established, with a consistent correlation between wound depth and TCA concentration. The clinical effects of medium-depth chemical peels are generally gratifying for both patient and physician.

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.