Evidence and consensus-based (S3) guidelines for the treatment of actinic keratosis: International League of Dermatological Societies in cooperation with the European Dermatology Forum: short version

BACKGROUND: Actinic keratosis (AK) is a frequent health condition attributable to chronic exposure to ultraviolet radiation. Several treatment options are available and evidence based guidelines are missing. OBJECTIVES: The goal of these evidence- and consensus-based guidelines was the development of treatment recommendations appropriate for different subgroups of patients presenting with AK. A secondary aim of these guidelines was the implementation of knowledge relating to the clinical background of AK, including consensus-based recommendations for the histopathological definition, diagnosis and the assessment of patients. METHODS: The guidelines development followed a pre-defined and structured process. For the underlying systematic literature review of interventions for AK, the methodology suggested by the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was adapted. All recommendations were consented during a consensus conference using a formal consensus methodology. Strength of recommendations was expressed based on the GRADE approach. If expert opinion without external evidence was incorporated into the reasoning for making a certain recommendation, the rationale was provided. The Guidelines underwent open public review and approval by the commissioning societies.RESULTS: Various interventions for the treatment of AK have been assessed for their efficacy. The consenting procedure led to a treatment algorithm as shown in the guidelines document. Based on expert consensus, the present guidelines present recommendations on the classification of patients, diagnosis and histopathological definition of AK. Details on the methods and results of the systematic literature review and guideline development process have been published separately. CONCLUSIONS: International guidelines are intended to be adapted to national or regional circumstances (regulatory approval, availability and reimbursement of treatments).(AU)

Evidence- and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis - International League of Dermatological Societies in cooperation with the European Dermatology Forum - Short version.

BACKGROUND: Actinic keratosis (AK) is a frequent health condition attributable to chronic exposure to ultraviolet radiation. Several treatment options are available and evidence based guidelines are missing. OBJECTIVES: The goal of these evidence- and consensus-based guidelines was the development of treatment recommendations appropriate for different subgroups of patients presenting with AK. A secondary aim of these guidelines was the implementation of knowledge relating to the clinical background of AK, including consensus-based recommendations for the histopathological definition, diagnosis and the assessment of patients. METHODS: The guidelines development followed a pre-defined and structured process. For the underlying systematic literature review of interventions for AK, the methodology suggested by the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was adapted. All recommendations were consented during a consensus conference using a formal consensus methodology. Strength of recommendations was expressed based on the GRADE approach. If expert opinion without external evidence was incorporated into the reasoning for making a certain recommendation, the rationale was provided. The Guidelines underwent open public review and approval by the commissioning societies. RESULTS: Various interventions for the treatment of AK have been assessed for their efficacy. The consenting procedure led to a treatment algorithm as shown in the guidelines document. Based on expert consensus, the present guidelines present recommendations on the classification of patients, diagnosis and histopathological definition of AK. Details on the methods and results of the systematic literature review and guideline development process have been published separately. CONCLUSIONS: International guidelines are intended to be adapted to national or regional circumstances (regulatory approval, availability and reimbursement of treatments).

Tattoo ink darkening of a yellow tattoo after Q-switched laser treatment.

The popularity of tattoos is burgeoning with 20-30 million tattooed individuals in the Western World. Requests for removal can be expected to rise concurrently with increased applications. Laser removal of tattoos is potentially a more cosmetically acceptable method of removing tattoos than surgical excision or dermabrasion. Nevertheless, complications and side-effects can result from laser treatment and include scarring, hypopigmentation, hyperpigmentation, partial removal, infection, bleeding and tattoo ink darkening. The latter has been reported for flesh-toned and red tattoos. Such a complication has never been reported for the laser treatment of a yellow tattoo in the dermatological literature. We describe a case of tattoo ink darkening of a yellow tattoo after treatment with the 532 nm quality-switched Neodymium : Ytrrium-Aluminium Garnet laser to highlight clinicopathological features. The mechanism by which some tattoos darken after laser treatment is not clearly understood. We review darkening of tattoos after laser treatment to raise awareness of this important complication. This paper will help to facilitate discussions with the patient and in obtaining informed consent prior to commencing treatment. Tattoo ink darkening of a yellow tattoo adds to the growing list of complications resulting from attempts at tattoo removal.

Mohs' micrographic surgery using frozen sections alone may be unsuitable for detecting single atypical melanocytes at the margins of melanoma in situ.

BACKGROUND: It remains questionable whether micrographic surgery with frozen sections is an appropriate technique for excision of melanoma in situ (MIS) of the lentigo maligna type. Advocates of the technique have interpreted MIS as being histologically defined by nests and contiguous atypical melanocytes on the basal layer. Others, however, have viewed the periphery of MIS as consisting of scattered single atypical melanocytes, a finding that may be difficult or impossible to establish on frozen sections. OBJECTIVES: To examine the reliability of micrographic surgery using frozen sections interpreted by an experienced Mohs' surgeon, in the excision of MIS. METHODS: From a total of 154 specimens, frozen sections from the 50 specimens with margins that were considered difficult to interpret were thawed, sent for routine processing and then examined 'blind' by a dermatopathologist. RESULTS: Using the dermatopathologist's report on paraffin-embedded sections as a reference point, the sensitivity and specificity of frozen sections were calculated to be 59% and 81%, respectively. CONCLUSIONS: Using these histological criteria, micrographic surgery with frozen sections alone is unreliable in the excision of MIS.

Clinical and histologic trends of melanoma.

BACKGROUND: Several changing clinical and histopathologic melanoma trends occurred from the 1950s to the 1980s. OBJECTIVE: The purpose of this study was to evaluate melanoma trends during the past decade and to compare present trends to those documented during the past four decades. METHODS: Sex, age at diagnosis, location, tumor thickness, stage, and histologic subtypes were evaluated from 1984 to 1995 and compared with trends during the past four decades. RESULTS: Most changing trends from the past four decades have slowed or stabilized during the past decade. CONCLUSION: Complete reporting of all melanomas to central tumor registries is necessary to accurately analyze present and future melanoma trends. Ongoing and new prevention and control strategies beginning at birth may be necessary to continue the positive efforts to curtail the melanoma epidemic.

Histopathologic changes of the eyelid skin following trichloroacetic acid chemical peel.

The use of trichloroacetic acid (TCA) as a periorbital and eyelid peel for skin rejuvenation is gaining significant acceptance among oculoplastic surgeons, dermatologists, and other surgery groups. In spite of the current enthusiasm, there remain potentially serious complications resulting from any periorbital peel. Cases of cicatricial ectropion have been reported in phenol-peeled patients, and lower eyelid ectropion has reportedly occurred in patients undergoing deep eyelid peel in conjunction with a blepharoplasty (1,2). To avoid this complication, it is necessary to better understand the depth of the wound produced by different strengths and combinations of peeling agents applied to living eyelid tissue and, more important, to determine the concentrations of TCA that are likely to lead to cicatricial ectropion when applied in a consistent fashion. We chose upper-eyelid skin because it is easier to obtain for histopathologic study than lower-eyelid skin and, in our experience, is more sensitive to hypertrophic changes after chemical peeling or carbon dioxide laser resurfacing. We applied TCA to the preseptal skin of 10 patients 48 h before standard upper-eyelid blepharoplasty. The acid was applied to produce a "frost," using varying concentrations of acid, ranging from 20 to 50%. The treated skin removed at the time of blepharoplasty was reviewed in a masked fashion by a dermatopathologist to determine the depth of necrosis. We found that superficial peels with necrosis involving 30% of the epidermis were produced by the lowest-concentration combination of TCA applied (20% followed by 0%). As the strength increased, so did the depth of peel. The combination of 50% followed by a second application of 50% produced the deepest peel, with necrosis into the papillary dermis. This finding would indicate that the chance of developing cicatricial ectropion with any of the tested combinations of TCA should be very remote.

Mohs micrographic surgery for the treatment of dermatofibrosarcoma protuberans. Results of a multiinstitutional series with an analysis of the extent of microscopic spread.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft-tissue tumor of the skin; its microscopic extent of invasion beyond the grossly visible tumor is frequently difficult to appreciate. Although wide local excision has been the standard treatment of DFSP, recurrence rates range from 11% to 53%. Because Mohs micrographic surgery allows the extent of excision to be tailored to the microscopic extent of tumor, we evaluated this technique for the treatment of primary and recurrent DFSP. OBJECTIVE: Our purpose was to determine the local recurrence rate and microscopic extent of spread of primary and recurrent DFSP after treatment with Mohs micrographic surgery. METHODS: The records of 58 patients with primary and recurrent DFSP treated with Mohs micrographic surgery at three institutions were reviewed and the macroscopic and microscopic extents of tumor were recorded. RESULTS: One patient with a twice-recurrent DFSP had another recurrence after Mohs micrographic surgery, for an overall local recurrence rate of 2% (zero for primary tumors and 4.8% for recurrent tumors). There were no cases of regional or distant metastases. Macroscopic tumor size ranged from 0.3 x 0.6 cm to 30 x 20 cm, whereas microscopic (postoperative) size ranged from 1.8 x 1.0 cm to 35 x 40 cm. We calculated the likelihood that a given width of excision around the macroscopic tumor would clear the entire microscopic extent of tumor. Standard wide excision with a width of 1 cm around the primary tumor would have left microscopic residual tumor in 70.7%; a width of 2 cm, 39.7%; 3 cm, 15.5%; and 5 cm, 5.2%. Even an excision width of 10 cm would not have cleared the microscopic extent of some tumors, despite taking a huge excess of normal tissue. CONCLUSION: Treatment of primary and recurrent DFSP by Mohs micrographic surgery results in a low recurrence rate because of the ability of the technique to permit the detection and excision of microscopic tumor elements in even the most asymmetric tumors. Whatever type of surgery is chosen to treat DFSP, it is necessary to assess the entire perimeter of the tumor for microscopic extension and to achieve tumor-free margins in all directions.

The nasofacial interpolated flap in reconstruction of the nasal ala.

BACKGROUND: Skin cancer frequently involves the nasal alae, the surgical reconstruction of which may be challenging if their margins, contours, and surface texture are to be preserved. OBJECTIVE: Our purpose was to describe our experience with a nasofacial interpolated flap in which a temporary bridging pedicle is used to transpose skin from the nasofacial and melolabial sulci to an alar defect. METHODS: The nasofacial interpolated flap was used in eight patients to reconstruct partial-thickness alar wounds after excision of a basal cell carcinoma. RESULTS: The functional and cosmetic outcome was excellent in five patients and is likely to be good in two others who had postoperative fullness of the flap inset. A poor result was seen in one patient, a heavy smoker, who healed with an atrophic scar at the margin of the primary defect. CONCLUSION: In alar wounds for which a full-thickness skin graft would provide inadequate bulk, the nasofacial interpolated flap transposes skin of excellent color and textural match without blunting the nasofacial sulcus or the alar groove.

Identification of common polymorphisms in the coding sequence of the human MSH receptor (MCIR) with possible biological effects.

The extension locus has been identified in many mammalian species as a gene that determines the relative amounts of eumelanin and phaeomelanin pigments in hair and skin. In at least three species, this locus has been demonstrated to encode the melanocyte-stimulating hormone receptor (MC1-R), and functionally variant alleles have been demonstrated to cause a broad range of pigmentation phenotypes. To test for MC1-R allelic variation in man, genomic DNA was extracted from skin samples collected from patients with different skin types (I-VI), and eye and hair color. A PCR-based approach was used to amplify the full-length coding sequence of the MC1-R and the resulting products were sequenced. Two polymorphic alleles were identified with single point mutations in the coding sequence: a valine-to-methionine substitution at position 92 (V92M), and an aspartic acid-to-glutamic acid substitution at position 84 (D84E). RFLP analysis demonstrated the presence of the V92M allele in 4 out of 60 (6.6%) of individuals examined, predominantly those with blue eyes and blond hair. This polymorphism was found in both heterozygous and homozygous states in individuals with type I skin. The D84E allele was found in one individual with skin type I; this person also has the V92 M allele and thus is a compound heterozygote.

Multimodal management of diffuse neonatal hemangiomatosis.

Diffuse neonatal hemangiomatosis is a rare, frequently fatal disorder. We describe the case of a neonate with numerous cutaneous and ocular hemangiomas. Hepatic hemangiomas were noted at 4 weeks of age, associated with congestive heart failure resulting from hepatic arteriovenous shunting. This condition was controlled by treatment with prednisone, interferon alfa-2b and hepatic embolization. Treatment of cutaneous hemangiomas with the tunable dye laser prevented hemorrhage, facilitated routine skin care, and allowed uninhibited intravenous access during hospitalization.

The Rieger flap for nasal reconstruction.

OBJECTIVE: To repair surgical defects of the middle and distal third of the nose. DESIGN: The anatomic and technical design of the Rieger (dorsonasal) flap is described. CONCLUSION: When performed on properly selected patients, the Rieger flap is an aesthetically predictable, one-stage procedure.

Reconstruction of midfacial defects following surgical management of skin cancer. The role of tissue expansion.

Compared with other locations on the face, skin cancer of the midface has a higher risk of recurrence owing, in part, to the mode of spread and the high frequency of subclinical extension. Skin cancers occurring in the region of the melolabial crease, nasal columella and medial canthus should be resected by Mohs surgery. Because tumors of the midface are sometimes recalcitrant, there are times when surgical ablation results in extensive defects. Reconstruction may be difficult owing to lack of available donor tissue, or because of previous surgery in the area of the proposed donor region. In these circumstances, tissue expansion in the form of controlled prolonged expansion or rapid intraoperative expansion, may, on occasion, provide the optimal reconstruction of form and function.

Chronic tissue expansion.

BACKGROUND: Chronic tissue expansion is an extremely useful addition to the dermatologic surgeon's skills. OBJECTIVE: To review chronic tissue expansion. METHODS: The relevant literature is summarized. Two case histories are presented as examples of the utility of chronic tissue expansion. RESULTS: The history of tissue expansion is briefly reviewed. Indications pertinent to the practice of dermatologic surgery are discussed. The devices themselves are described, as well as new experimental advances. The general procedure for utilizing tissue expanders is outlined, as well as relevant histologic changes that occur in expanded skin. Both common and rare complications are covered, with attention to prevention. CONCLUSION: Chronic tissue expansion provides an excellent means for obtaining extra tissue for cosmetic and reconstructive surgery.

Assessment of survival and microscopic changes in porcine skin flaps undergoing immediate intraoperative tissue expansion.

The technique of rapid intraoperative tissue expansion has been used with increasing frequency in the clinical setting over the last several years. This technique takes advantage of the skin's ability to immediately stretch and increase in surface area when expanded under a constant load. Sixteen random-pattern, rapidly expanded skin flaps on 10 domestic male pigs were studied to assess the predictive value of the fluorescein test for flap viability after rapid intraoperative tissue expansion. Partial fluorescence was found to be a more accurate predictor of flap survival in the experimental rapidly expanded flaps when compared to full fluorescence. Partial fluorescence was found to under-predict flap survival by 0.3 to 0.5 cm, whereas full fluorescence was found to under-predict flap survival by 2.5 cm. Additionally, histologic and ultrastructural changes were examined in rapidly expanded skin from the hip region in three pigs. The only microscopic change noted between control and experimental flaps was dilated capillaries in the dermis of expanded skin, which was noted by electron microscopy. Collagen and elastic tissue changes were not demonstrated in rapidly expanded pig skin by electron microscopy, direct immunofluorescence, collagen, and elastic tissue stains.

Clinical experience with Tc-99m labeled (N2S2) anti-melanoma antibody fragments and single photon emission computed tomography.

We evaluated the imaging capability of murine Tc-99m-labeled antimelanoma Fab fragments in 12 patients with clinical stage II and III melanoma. Tc-99m-NRX118.7 antimelanoma Fab fragment, 10.0 to 27.2 mCi (370-1, 006 MBq), was injected IV 30 min after irrelevant nonspecific intact antibody and 5 min after intact specific antibody were given. In all patients, whole-body scans and spot views were obtained. Single photon emission computed tomography (SPECT) was additionally performed in eight of the patients. The procedure was well tolerated, and 31 of 38 known foci of melanoma were detected (sensitivity, 82%). SPECT aided in detecting and better localizing lesions in the head, neck, and chest. The specificity of the technique was satisfactory when interpretation was performed with a knowledge of normal sites of accretion and excretion of technetium-99m activity such as the kidneys and gut. In several instances, lesions were discovered by means of the antibody scan before detection by other methods, and in two instances, the lack of visualization on antibody scan of a palpable mass correctly indicated that no melanoma was present in the mass. Scan results in three patients led to alterations in patient care; including preventing aggressive surgical and nonsurgical treatments. Although these data are encouraging, evaluation in additional patients will be essential to determine the clinical utility of this antibody scan in the management of patients with melanoma.

Squamous cell carcinoma of the skin (excluding lip and oral mucosa).

The striking impression obtained from reviewing the cancer literature is how difficult it is to analyze the data for answers to many important biologic, behavioral, prognostic, and therapeutic questions about squamous cell carcinoma of the skin. This article addresses current concepts, controversies, and management of cutaneous squamous cell carcinoma (excluding the lip and oral mucosa).

Treatment of keratoacanthomas with intralesional methotrexate.

Multiple modalities exist for the treatment of keratoacanthoma. Excisional surgery is currently the treatment of choice for the majority of keratoacanthomas. This can result in functional and cosmetic defects when large or strategically located lesions are treated. An effective nonsurgical treatment would be desirable in such cases. Intralesional therapy, particularly with 5-fluorouracil, has been shown to be effective in the treatment of keratoacanthomas. Systemic methotrexate has been tried, with variable success. We report an open, noncontrolled study of nine consecutive patients with unusually large or strategically located solitary keratoacanthomas treated successfully with intralesional methotrexate. All lesions responded promptly, with complete resolution after a mean of 3.0 weeks and a mean of 1.7 injections. No side effects occurred, and scarring was minimal. We concluded that intralesional methotrexate is a simple and effective modality for the treatment of select keratoacanthomas and may offer greater efficacy, a more rapid response, decreased pain, and lower cost compared with intralesional 5-fluorouracil.

Aggressive-growth basal cell carcinoma in young adults.

Aggressive-growth basal cell carcinoma (AG-BCC) defines a group of basal cell cancers that are histologically and clinically aggressive. This group includes morpheaform, infiltrating, and recurrent BCCs. Because of the clinical observation that the incidence of AG-BCC may be increased in patients under 35 years of age, compared with those older, we performed a retrospective study. We reviewed the pathologic findings of 3381 patients diagnosed with BCC, including 102 patients with BCC referred for Mohs surgery to determine whether AG-BCC occurs with increased frequency in patients younger than than 35 years of age. Among patients under 35 years of age, 38% of women had AG-BCC compared with 9% of women in the older age group. Similarly, 25% of men under 35 years of age had AG-BCC compared with 11% among men in the older age group. Aggressive-growth BCC is more frequently noted in patients under 35 years of age than in those older. Failure to diagnose this type of BCC, which may be clinically subtle, may lead to incomplete or inadequate treatment. Because of the tendency of these tumors to recur, greater long-term morbidity may result.

Changing trends in melanoma treatment and the expanding role of the dermatologist.

As the incidence of melanoma continues to increase, so does the role of the dermatologist as both medical and surgical oncologist for these patients, especially those with stage I disease. The dermatologist holds a key role in all phases of care, including prevention, diagnosis, treatment, and follow-up. The dermatologist is best trained to complete a full and thorough skin examination and is best able to recognize a melanoma at its earliest stages of radial growth. In large part because of advances in dermatology, the dysplastic nevus syndrome has been identified as an important marker and precursor lesion for melanoma; the dermatologist has the best knowledge base for the recognition and management of both sporadic and familial dysplastic nevi. Dermatologists also have the unique opportunity (by virtue of their patient population concerned with skin problems) to prevent melanoma through patient education concerning sun protection, self-examinations, and the ABCDs of melanoma recognition. The dermatologist is well trained to obtain an appropriate, full-thickness skin biopsy specimen and is also knowledgeable to interpret the pathologist's report, understanding the significance of the various histologic prognostic indices. Because of the changing trends in excisional margin size and fewer recommendations for ELND, the dermatologist is becoming more active in the surgical management of melanoma patients. In the MDMC, the dermatologist was clearly recognized as a capable surgeon to perform the wide local excisions for stage I patients. Almost one half of the patients seen (49%) were surgically treated in the department of dermatology. Of group I patients, 78% were treated by dermatologists. The dermatologist as surgeon should be capable of performing a wide local excision to the level of deep subcutaneous tissue or muscle fascia with an appropriate primary layered closure, local flap, or graft. Our experience confirms that the majority of patients present with local disease and a thin Breslow depth and thus can be skillfully treated in an outpatient setting under local anesthesia by a dermatologic surgeon. In follow-up, the dermatologist should provide continuity of care and should be knowledgeable in appropriate interval examinations and tests. The dermatologist is thoroughly skilled at the cutaneous examination and has the knowledge base to perform a careful and competent lymph node examination. As primary medical oncologist to these patients, the dermatologist needs to recognize stage II and stage III disease and be able to comprehensively discuss with the patient the options for treatment and how they affect their prognosis.(ABSTRACT TRUNCATED AT 400 WORDS)