National utilization patterns of Mohs micrographic surgery for invasive melanoma and melanoma in situ.

BACKGROUND: Although wide local excision continues to be commonly used for melanoma treatment, Mohs micrographic surgery (MMS) for the treatment of melanomas remains controversial. OBJECTIVE: We sought to determine national utilization patterns for MMS in the treatment of invasive melanoma and melanoma in situ. METHODS: A retrospective analysis of patients receiving surgical excision (MMS or wide local excision) for the treatment of invasive melanoma and melanoma in situ was performed using data from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program. RESULTS: A total of 195,768 melanomas were diagnosed from 2003 through 2009 from the 17 SEER registries. Utilization of MMS for invasive melanoma and melanoma in situ increased by 60% from 2003 to 2008. Of all SEER-captured lesions treated by surgical excision in this time period, 3.5% (6872) were excised by MMS. LIMITATIONS: Patient insurance status, physician reimbursement practices, and health care provider type were not addressed in this article. CONCLUSION: Use of MMS for melanoma appears to be increasing. Future studies should explore whether this is associated with better outcomes.

Patients with drug-eluting stents and management of their anticoagulant therapy in cutaneous surgery.

Whether a patient has a drug-eluting stent (DES) implanted may not seem to be an immediate concern for a dermatologist. However, the clinician needs to consider a patient's risk of bleeding if a patient is to undergo a cutaneous surgical procedure. Patients with skin cancer are generally older with a higher risk of comorbidities such as cardiovascular disease with history of cardiac stent implantation. After DES placement, patients are typically on long-term dual antiplatelet therapy, which increases the risk of bleeding. However, stopping antiplatelet therapy prematurely can lead to serious thrombotic complications. Thus, when performing a dermatologic procedure in a patient with a DES, the physician must weigh the risks of bleeding complications with continuing antiplatelet therapy against the risk of thrombotic complications associated with stopping antiplatelet therapy. The aim of this review is to identify the issues for the dermatologist and the dermatologic surgeon surrounding the perioperative treatment of patients with a DES and to discuss the treatment of patients with an implanted DES.

Catastrophic cutaneous carcinomatosis in the non-organ transplant patient.

BACKGROUND: The increased frequency of nonmelanoma skin cancers (NMSCs) in organ transplant recipients has been termed "catastrophic cutaneous carcinomatosis" (CCC). We have treated a cohort of immunocompetent patients with an increased number of NMSCs that meets the definition of CCC whom we have termed "catastrophic cutaneous carcinomatosis-immunocompetent" (CCC-IC). OBJECTIVE: We sought to further understand the epidemiologic characteristics of this subset of immunocompetent patients with a high burden of NMSCs. METHODS: Our pathology database was searched over a 4-year experience of a Mohs surgeon to identify patients with greater than 10 basal cell carcinomas (BCCs) and/or squamous cell carcinomas (SCCs) in a 12-month period who had no underlying systemic cause of immunosuppression or genetic predisposition to form NMSCs. Information regarding the 13 patients who met inclusion criteria was collected by questionnaire and analyzed. RESULTS: There was no statistically significant difference in the constitutional variables of this patient population. Patients with CCC-IC had a SCC:BCC ratio of 2.5:1, similar to what is seen in organ transplant recipients where the SCC:BCC ratio is 2:1 with SCC predominance. There was a statistically significant increase in the number of SCCs in patients with CCC-IC (8.77/patient) as compared with control patients (2.27/patient). Most strikingly, a 13.8-fold higher incidence of malignant melanoma in the CCC-IC group was found as compared with the general population. LIMITATIONS: Limitations to this study include a small sample size and recall bias. CONCLUSION: Our data suggest that patients with CCC-IC have skin cancer profiles of SCC and BCC similar to organ transplant recipients and have a markedly higher incidence of malignant melanoma than the general population. These patients require strict monitoring and combination therapeutic approaches toward management of cutaneous carcinomas.

Acquired cutis laxa following urticarial vasculitis associated with IgA myeloma.

Cutis laxa (CL) is an inherited or acquired connective tissue disorder characterized clinically by loosely hanging skin folds. There is often preceding cutaneous inflammatory eruption (ie, urticaria, eczema, erythema multiforme), and there is frequently internal organ involvement of the gastrointestinal, urogenital, pulmonary, and cardiovascular systems. Histologically, there are degenerative changes in the dermal elastic fibers. Of the few reports on this rare disorder, authors have speculated about an immune-mediated destruction of elastic fibers, and monoclonal gammopathies, such as multiple myeloma or heavy chain deposition disease, have a recognized association with CL. We report an unusual case of rapidly progressing acquired CL associated with leukocytoclastic vasculitis, IgA myeloma, and an immune complex-mediated glomerulonephritis. Light microscopy of the lax skin revealed complete absence of elastic fibers in areas of vasculitis.

Mohs micrographic surgery and surgical excision for nonmelanoma skin cancer treatment in the Medicare population.

OBJECTIVES: To identify Medicare use rates of Mohs micrographic surgery (MMS) and surgical excision for the treatment of nonmelanoma skin cancer (NMSC) and to identify patient, lesion, and geographic characteristics associated with treatment type. DESIGN: A retrospective analysis of Medicare beneficiaries. SETTING: Surveillance, Epidemiology, and End Results database. PATIENTS: Patients undergoing MMS or other surgical intervention for the treatment of NMSC from January 1, 2001, through December 31, 2006. MAIN OUTCOME MEASURES: Surgical treatment, patient, and lesion characteristics. RESULTS: A total of 26,931 operations were performed for the treatment of NMSC from 2001 through 2006, of which 36.4% were MMS. Although the rate of surgical excision slightly increased during this period (1.8 vs 2.1 per 100 Medicare beneficiaries), the rate of MMS doubled (0.75 vs 1.5 per 100 Medicare beneficiaries). In 46.9% of facial lesions, MMS was performed, whereas MMS was used to treat 14.7% of total body lesions. Atlanta, Georgia, had the highest proportion of patients treated with MMS (45.1%); Louisiana had the lowest (11.0%). Age, race, lesion location, and area of country for patient treatment were significantly associated with MMS use (all P < .001). CONCLUSIONS: Surgical treatment of NMSC increased substantially from 2001 through 2006, primarily because of a doubling in the rate of MMS procedures. Significant differences in surgical rates, depending on patient age, race, lesion location, and geographic region, of treatment were found.

A rare case of multiple segmental eccrine spiradenomas.

Eccrine spiradenoma is a benign adnexal neoplasm that has been historically designated as a tumor of eccrine differentiation, although current reconsideration indicates an apocrine process. It usually presents on the trunk and extremities as a tender dermal or subcutaneous papule or nodule frequently with a pink or blue hue. The clinical picture is often not distinct and biopsy is required for diagnosis. Eccrine spiradenoma can present in a variety of ways, including as tumors arranged in zosteriform/dermatomal and/or blaschkoid distributions, often precluding a straightforward diagnosis. Proper diagnosis of eccrine spiradenoma is important due to the occurrence of potentially life-threatening malignant transformation. This article illustrates a rare presentation of eccrine spiradenoma with a concise review for the dermatologist.

Anticonvulsant hypersensitivity syndrome associated with Bellamine S, a therapy for menopausal symptoms.

Anticonvulsant hypersensitivity syndrome (AHS) is a rare, potentially fatal, idiosyncratic drug reaction characterized by fever, morbilliform rash, lymphadenopathy, hepatitis, and hematologic abnormalities. Aromatic antiepileptic agents, such as phenytoin, carbamazepine, and phenobarbital are the most frequent causes of this syndrome. We report a case of a previously healthy, postmenopausal woman who developed anticonvulsant hypersensitivity syndrome while taking Bellamine S (belladonna alkaloids; ergotamine; phenobarbital) for hot flashes. Although combinations of belladonna, ergotamine, and phenobarbital have been used for medical treatment of menopausal symptoms since the 1960s, this is the first known case report of its association with anticonvulsant hypersensitivity syndrome. Given the current debate about the risks of hormonal replacement therapy, more women are seeking alternative therapies for menopausal symptoms. Dermatologists need to be aware of this potential serious reaction to this phenobarbital-containing therapy for hot flashes.

Coevolutionary patterns in plasminogen activation.

The generation of plasmin by plasminogen (Pg) activators (PAs) is a physiologic process in animals that dissolves blood clots and promotes wound healing, blood vessel growth, and the migration of normal and cancerous cells. Pathogenic bacteria have evolved PAs [e.g., streptokinase (SK) and staphylokinase] that exploit the Pg system to infect animals. Animal PAs have a conserved ability to cleave a wide spectrum of animal Pgs, but the ability of bacterial PAs to cleave different animal Pgs is surprisingly restricted. We show that the spectrum of activity of an archetypal bacterial PA (SK) with animal Pgs can be profoundly altered by mutations that affect intermolecular complementarity at sites that participate in complex formation or substrate binding. Comparative sequence analysis of animal plasmins vs. close structural homologues (trypsin and chymotrypsin) that are not molecular targets for invading bacteria indicates that the sites in plasmin that interact with SK are preferentially targeted for mutation. Conversely, intermolecular contact sites in SKs that activate human Pg are more highly conserved than other loci in the molecule or than the same sites in other SKs that activate non-human Pgs. We propose that active modulation of intermolecular complementarity at sites of contact between SK and Pg may represent a competitive evolutionary strategy in a survival battle, whereby animals seek to evade bacterial invasion, and bacteria endeavor to invade their animal hosts.

Structural elements that govern the substrate specificity of the clot-dissolving enzyme plasmin.

There is remarkable homology between the core structures of plasmin, a fibrin clot-degrading enzyme, and factor D, a complement-activating enzyme, despite markedly different biological functions. We postulated that sequence divergence in the loop structures between these two enzymes mediated the unique substrate and inhibitor interactions of plasmin. Recombinant microplasminogens chimerized with factor D sequences at loops 3, 5, and 7 were cleaved by the plasminogen activator urokinase and developed titratable active sites. Chimerization abolished functional interactions with the plasminogen activator streptokinase but did not block complex formation. The microplasmin chimeras showed enhanced resistance (k(i) decreased up to two to three times) to inactivation of microplasmin by alpha(2)-antiplasmin. Microplasmin chimerization had minimal ( approximately 2 fold) effects on the catalytic efficiency for cleavage of small substrates and did not alter the cleavage of fibrin. However, microplasmin and the microplasmin chimeras showed enhanced abilities to degrade fibrin in plasma clots suspended in human plasma. These studies indicate that loop regions of the protease domain of plasmin are important for interactions with substrates, regulatory molecules, and inhibitors. Because modification of these regions affected substrate and inhibitor interactions, loop chimerization may hold promise for improving the clot dissolving properties of this enzyme.

Chimerism reveals a role for the streptokinase Beta -domain in nonproteolytic active site formation, substrate, and inhibitor interactions.

Streptokinase (SK) and staphylokinase form cofactor-enzyme complexes that promote the degradation of fibrin thrombi by activating human plasminogen. The unique abilities of streptokinase to nonproteolytically activate plasminogen or to alter the interactions of plasmin with substrates and inhibitors may be the result of high affinity binding mediated by the streptokinase beta-domain. To examine this hypothesis, a chimeric streptokinase, SKbetaswap, was created by swapping the SK beta-domain with the homologous beta-domain of Streptococcus uberis Pg activator (SUPA or PauA, SK uberis), a streptokinase that cannot activate human plasminogen. SKbetaswap formed a tight complex with microplasminogen with an affinity comparable with streptokinase. The SKbetaswap-plasmin complex also activated human plasminogen with catalytic efficiencies (k(cat)/K(m) = 16.8 versus 15.2 microm(-1) min(-1)) comparable with streptokinase. However, SKbetaswap was incapable of nonproteolytic active site generation and activated plasminogen by a staphylokinase mechanism. When compared with streptokinase complexes, SKbetaswap-plasmin and SKbetaswap-microplasmin complexes had altered affinities for low molecular weight substrates. The SKbetaswap-plasmin complex also was less resistant than the streptokinase-plasmin complex to inhibition by alpha(2)-antiplasmin and was readily inhibited by soybean trypsin inhibitor. Thus, in addition to mediating high affinity binding to plasmin(ogen), the streptokinase beta-domain is required for nonproteolytic active site generation and specifically modulates the interactions of the complex with substrates and inhibitors.