Variation in the diagnosis and clinical management of lentigo maligna across Europe: a survey study among European Association of Dermatologists and Venereologists members.

BACKGROUND: Lentigo maligna (LM), a form of melanoma in situ, is treated to prevent progression to lentigo maligna melanoma (LMM). Surgical treatment is the gold standard. However, treatment guidelines are based on expert opinion, and comparative studies are lacking. OBJECTIVE: The objective of this study was to assess the diagnostic methods and clinical management of LM patients among European dermatologists and residents. METHODS: A survey consisting of 29 questions about diagnostic methods and treatment options used for LM patients was sent to 3308 members of the European Association of Dermatologists and Venereologists (EADV). RESULTS: Most questions were multiple choice, and multiple answers could be ticked per question. A total of N = 415 (12.5%) completed surveys were included in the analyses. A combination of clinical diagnosis (65.7%), dermatoscopy (83.4%) and histopathology (88.2%) is used by most respondents to diagnose LM. Tissue for histopathological evaluation was collected most often using a single punch biopsy in 61.0%. The most common treatment for LM patients <60 years of age is surgery (97.6%). For LM patients >70 years of age, 66.8% of the respondents preferred surgical treatment. Non-surgical options such as radiotherapy (17.0%), topical imiquimod (30.6%), watchful waiting (19.6%) or cryotherapy (20.4%) were used in this elderly group. Subanalysis showed that respondents who take into account patient preference used topical imiquimod, radiotherapy and watchful waiting more often. CONCLUSION: In conclusion, the results of this survey show that there is a variance in the diagnostic methods and treatment modalities used for LM across Europe. Surgery remains the most utilized option. However, non-surgical options, such as topical imiquimod and radiotherapy, are most often used for elderly patients. We recommend that future studies focus on patient preference and compare surgical to non-surgical therapy.

[A baby with progressive skin lesions on the scalp]. / Een baby met toenemende huidafwijkingen op de scalp.

An eight-month-old girl was referred to the dermatologist with a progressive desquamative and purulent eruption on the scalp. Laboratory tests confirmed the diagnosis kerion celsi and the girl was successfully treated with an antimycoticum. Kerion celsi is a deep inflammatory fungal infection on the scalp. Early diagnosis is essential to prevent irreversible hair loss.

A systematic review on the role of imiquimod in lentigo maligna and lentigo maligna melanoma: need for standardization of treatment schedule and outcome measures.

Lentigo maligna (LM) is an in situ variant of melanoma. Our objective was to systematically review clinical and histological clearance and recurrence rates of imiquimod treatment of LM with emphasis on progression to lentigo maligna melanoma (LMM). PubMed, EMBASE and the Cochrane library were searched from inception to May 2015. Articles were included if they described histologically proven LM treated with imiquimod 5% monotherapy or combined with another topical therapy. Analysed outcomes were clinical and histological clearance, recurrence rates and number of LMM. The quality was assessed using the GRADE-like checklist, and results were reported according to the PRISMA Statement. Twenty-six case reports, 11 retrospective studies, three prospective studies and one randomized controlled trial were included. One case report of poor quality was excluded. Complete clinical clearance was seen in 369 of 471 patients (78.3%). Histological clearance was present in 285 of 370 (77%) patients. LMM was diagnosed in nine (1.8%) patients 3.9 months (range 0-11 months) post-treatment. Univariate multinominal logistic regression showed that 6-7 applications/week had a 6.47 greater odds (P = 0.017) of resulting in complete clinical clearance compared to 1-4 applications/week. An intensity of 6-7 applications/week showed a 8.85 greater odds (P = 0.003) of resulting in histological clearance compared to 1-4 applications. Applying imiquimod >60 times during a treatment period of 12 weeks (range 4-36) showed a 7.75 greater odds (P = 0.001) of resulting in histological clearance compared to <60 total applications. In conclusion, a treatment schedule using imiquimod 6-7 applications per week, with at least 60 applications, shows the greatest odds of complete clinical and histological clearance of LM. Imiquimod is an option for patients unfit for or not willing to undergo surgery or radiotherapy. Nine cases of LM progressed to LMM shortly after treatment. Our hypothesis is that these LMM may have been present before starting imiquimod.

Current treatment methods for combination antiretroviral therapy-induced lipoatrophy of the face.

Combination antiretroviral therapy (CART) reduces the mortality and morbidity in HIV-infected patients. However, facial lipoatrophy (FLA) is one of the well-known side-effects of this treatment and subsequently imposes major problems for HIV-infected patients. In the last decade, ample experience has been obtained with both local therapeutic options as well as possible systemic treatment options. Soft tissue fillers are a relatively simple and efficient treatment option for FLA. Especially, the biodegradable semi-permanent fillers combine a good effect with durability and an acceptable safety profile. The best way to prevent or restrict the development of FLA remains the exclusion of thymidine analogue nucleoside reverse-transcriptase inhibitors from the CART schedule.

Botryomycosis in an HIV-positive subject.

A 28-year-old male AIDS patient with generalized painful skin ulcers, fever and malaise presented to us. The differential diagnosis included varicella zoster infection, herpes simplex infection, actinomycosis, sporotrichosis and botryomycosis. Histopathology revealed clusters of gram-positive coccoid bacteria in the deep dermis, surrounded by a mixed dense inflammatory infiltrate. A bacterial culture grew Staphylococcus aureus. Viral cultures remained negative. Based on these findings botryomycosis was diagnosed. Large lesions were excised surgically and with antimicrobial therapy all skin symptoms disappeared. We discuss this case with reference to a short review of the literature on botryomycosis in relation to HIV infection.

Treatment of necrobiosis lipoidica with topical psoralen plus ultraviolet A.

BACKGROUND: Necrobiosis lipoidica (NL) is a rare skin disease, mostly seen on the legs and often occurring in patients with diabetes mellitus. The disease belongs to the idiopathic cutaneous palisading granulomatous dermatitides associated with a degeneration of collagen, thus leading to skin atrophy. Application of topical corticosteroids is the most widely used treatment but the results are not always satisfactory and may worsen skin atrophy. Preliminary studies in patients with NL have shown a clinical response with psoralen plus ultraviolet (UV) A (PUVA). Objectives To study the effect of topical PUVA on NL in a multicentre prospective study. METHODS: Thirty patients (27 women and three men) including 13 with insulin-dependent diabetes mellitus, with a diagnosis of NL proven by histopathology, were included. All patients had been unsuccessfully treated with topical and/or intralesional corticosteroids. Patients were treated twice weekly with an aqueous gel containing 0.005% psoralen followed by irradiation with UVA. Clinical photographs were taken for evaluation. In addition, 20-MHz high-frequency ultrasound analysis was performed in 10 patients to evaluate the thickness and density of the dermis during topical PUVA therapy. RESULTS: Five patients (17%) showed complete clearing (healing of ulceration and disappearance of erythema) after a mean of 22 exposures (range 15-30). Eleven patients (37%) showed improvement, defined as healing of ulceration and/or reduction of erythema, after a mean of 23 exposures (range 11-42). Ten patients (33%) showed no effect and four patients (13%) worsened during topical PUVA therapy. The treatment results of the patients who suffered from diabetes mellitus were not different from those who did not have diabetes mellitus. No difference was seen in mean dermal thickness (1666 vs. 1706 micro m) and density (17 vs. 16 units) before and after topical PUVA therapy. Side-effects were seen in 10 patients: hyperpigmentation (n = 4), blistering (n = 4) and bacterial infection (n = 2). CONCLUSIONS: Topical PUVA may be a useful treatment modality for NL in patients not responding to topical or intralesional corticosteroids.

[Diagnostic image (41). Molluscum contagiosum]. / Diagnose in beeld (41). Molluscum contagiosum.

An 18-year-old woman presented with solitary molluscum contagiosum in the skin of the thorax.

Treatment of patients with systemic sclerosis with extracorporeal photochemotherapy (photopheresis).

BACKGROUND: Effective treatment modalities for systemic sclerosis, a life-threatening and disabling disease, are still lacking. Possible efficacy of photopheresis has been reported in several studies. Because of the complexity of the treatment, placebo-controlled trials are difficult to perform. OBJECTIVE: We investigated the effect of photopheresis on clinical parameters (skin score and internal organ functions), immunologic parameters, and quality of life. METHODS: Nineteen patients with progressive systemic sclerosis of less than 5 years' duration were randomized into 2 groups. One group (group A) received photopheresis for 1 year, the other group (group B) received no treatment at all. After 1 year the groups switched (crossover design). Photopheresis was performed on 2 consecutive days every 4 weeks; the psoralens were administered parenterally. The main outcome parameter was the skin score after 1 year of treatment compared with that of the control group. RESULTS: The average skin score improved with 5.4% (standard error [SE], 20. 8%) in group A and deteriorated with 4.5% (SE, 13.8%) in group B (not significant; P =.71). Before crossover, the average increase in skin score was 5.3% (means of entire group). No change was observed in other clinical parameters. Approximately 1 year after crossover, the skin score reversed to what would have been expected with an average increase of 5.3% per year. There was also no effect on immunologic parameters. Quality of life did not change during treatment. CONCLUSION: We were not able to show that photopheresis, performed as described above, is an effective treatment in systemic sclerosis. The difference in average skin score was statistically and clinically insignificant. Despite the small sample size, we concluded that the magnitude of the observed changes is too small to justify photopheresis as a regular treatment.

Adhesion molecule expression in basal cell carcinoma.

Basal cell carcinomas (BCCs) are frequently associated with a peritumoral mononuclear infiltrate. Until now, the function of this inflammatory infiltrate and its possible role in the control of tumor growth is unclear. Mechanisms controlling endothelial and target cell adhesiveness for leukocytes are important features in the development of a specific local immune response. The expression and distribution of the adhesion molecules ICAM-1, VCAM-1 and E-selectin by microvascular endothelial cells and tumor cells, together with their leukocyte receptors LFA-1, VLA-4 and CLA respectively, were studied in 33 BCCs of different histological subtypes. In normal skin, ICAM-1 is expressed by resting endothelial cells, whereas VCAM-1 and E-selectin expression correlates with endothelial activation. The epidermis in normal conditions displays no ICAM-1, VCAM-1, or E-selectin expression. In BCC, endothelial ICAM-1 expression was only slightly increased compared to normal skin, whereas expression of endothelial VCAM-1 and E-selectin was low or absent in all BCCs examined. Peritumoral infiltrates contained mostly LFA-1-expressing lymphocytes, with minimal VLA-4 and CLA positivity. In none of the cases studied was adhesion molecule expression by BCC tumor cells identified. The lack of significant expression of adhesion molecules on peritumoral vascular endothelial cells and BCC tumor cells does not support the idea of specific, cell-mediated immunity being an important mechanism in limiting BCC tumor spread.

Transforming growth factor-beta and bcl-2 distribution patterns distinguish trichoepithelioma from basal cell carcinoma.

BACKGROUND: Trichoepithelioma (TE) and basal cell carcinoma (BCC) have many features in common both clinically and histologically. Despite these many similarities TE and BCC represent different biological entities. OBJECTIVE: Recently, bcl-2 and CD34 have been reported as reliable markers in distinguishing the two types of tumor. Transforming growth factor-beta (TGF-beta), a multifunctional regulator of both cell growth and differentiation, was evaluated in this study. METHODS: The immunohistochemical expression of TGF-beta was compared with the distribution patterns of bcl-2 and CD34 in five BCCs, five TEs, and seven borderline cases. RESULTS: All five TEs showed a diffuse cytoplasmic staining of tumor cells for TGF-beta, whereas four of five BCCs were TGF-beta negative. Of the seven equivocal cases of TE/BCC, five tumors demonstrated TGF-beta positivity in combination with negative bcl-2 staining corresponding to TE. The remaining two cases demonstrated the opposite staining pattern, characteristic for BCC. CONCLUSION: The TGF-beta staining pattern appears to be a helpful additional marker together with bcl-2 in differentiating between TE and BCC. The demonstrated staining differences may relate to the distinct origin and biological behavior of the two tumors and may therefore be of value in subsequent patient management.

Expression of adhesion molecules in pagetoid reticulosis (Woringer-Kolopp disease).

Cell adhesion molecules play a critical role in lymphocyte migration and homing. They convey tissue-specific homing properties to lymphocyte subsets and regulate the positioning of these subsets in the body. In a patient with pagetoid reticulosis, a rare form of cutaneous T-cell lymphoma characterized by extreme epitheliotropism, we examined the expression of adhesion molecules. The neoplastic T lymphocytes showed a strong expression of cutaneous lymphocyte antigen, a skin-homing receptor which interacts with E-selectin on skin endothelium. alpha E beta 7 an adhesion molecule interacting with E-cadherin on epithelial cells, was also expressed on tumour cells. These findings suggest that adhesion molecules are responsible for the unique growth pattern in pagetoid reticulosis, and for the clinical behaviour of the disorder.

Quantification of cutaneous sclerosis with a skin elasticity meter in patients with generalized scleroderma.

BACKGROUND: The skin score, a subjective assessment of skin elasticity, is widely used in patients with systemic sclerosis. Although this scoring method is regarded as a validated and accepted tool, the interobserver and intraobserver reproducibility is relatively poor. OBJECTIVE: Our purpose was to investigate whether the recently developed SEM 474 cutometer, which exerts a controlled vacuum force to the skin, can measure skin elasticity more objectively than the skin score. METHODS: Skin elasticity was measured in 74 different body areas in patients with systemic sclerosis and compared with the skin score obtained from the same areas. RESULTS: The cutometer produced quantitative and reproducible data. A large-diameter (8 mm) measuring probe was superior to a small probe. The interobserver intraclass correlation coefficient (ICC) was 0.92; the intraobserver ICC was 0.94. A linear correlation was found with the clinical skin score; the Spearman rank correlation test was 0.69. CONCLUSION: The correlation with the skin score was reasonable, despite the observation that regional differences in skin elasticity were detected by the cutometer but not by the human observer, who automatically compensates for these factors and integrates them into the skin score. The high interobserver and intraobserver ICC makes the cutometer more suitable for quantifying changes in skin thickness than the subjective skin score.

Systemic anti-tumor necrosis factor antibody treatment exacerbates endotoxin-induced uveitis in the rat.

Tumor necrosis factor is released in the circulation and aqueous humor during endotoxin-induced uveitis, and induces acute uveitis when injected intraocularly in rats. To elucidate the role of tumor necrosis factor in the development of endotoxin-induced uveitis we analysed the effect of neutralizing anti-tumor necrosis factor antibodies and of pentoxifylline, a drug that inhibits tumor necrosis factor synthesis. Lewis rats were treated with: (a) a single intracardial injection of polyclonal rabbit anti-murine tumor necrosis factor antiserum prior to foot pad injection of 200 micrograms lipopolysaccharide; (b) an intraperitoneal injection of 10 mg pentoxifylline 1 hr before, at the time of, and 3 hr after foot pad injection of lipopolysaccharide; or (c) an intravitreal injection of 20 to 500 micrograms pentoxifylline together with 1 microgram lipopolysaccharide. The ocular inflammation was examined by slit-lamp and evaluated for the presence of hyperemia, flare, miosis, infiltrating cells or hypopyon. Levels of tumor necrosis factor in serum and aqueous samples were determined using a bioassay. Systemic treatment with either anti-tumor necrosis factor antibodies or pentoxifylline resulted in a significant inhibition, 90 and 70% respectively, of serum tumor necrosis factor activity at 3 to 4 hr after lipopolysaccharide injection. Systemic pentoxifylline treatment had no influence on the severity of uveitis. Anti-tumor necrosis factor antibody treatment, in contrast, caused an exacerbation of endotoxin-induced uveitis at t = 20 hr; mean uveitis score 3.9 vs. 1.4 in controls; P < 0.01. Intraocular administration of pentoxifylline together with lipopolysaccharide also had an aggravating effect on uveitis, that was associated with increased levels of intraocular tumor necrosis factor. The results show that inhibition of serum tumor necrosis factor activity does not block the development of endotoxin-induced uveitis. In fact, anti-tumor necrosis factor antibody treatment exacerbates the intraocular inflammation. These findings suggest that tumor necrosis factor may have other than proinflammatory properties in this uveitis model.

Demodicidosis or rosacea: what did we treat?

We report a 75-year-old man with a fulminant rosacea-like eruption, suggestive of demodicidosis. Multiple Demodex folliculorum mites were found in facial scales and pustules and, on histological examination, in the infundibulum of pilosebaceous follicles and in the dermis. Intradermal mites were surrounded either by polymorphonuclear granulocytes and histiocytes, or by a granulomatous infiltrate containing foreign-body giant cells, which had phagocytosed the parasites. Complete recovery, with disappearance of facial mites, was achieved by treatment with a combination of oral and topical metronidazole, although this drug is not known to be miticidal.

Tumour necrosis factor-induced uveitis in the Lewis rat is associated with intraocular interleukin 6 production.

Lewis rats were injected with recombinant murine tumour necrosis factor-alpha either intravitreally (0.08-50 ng) or intracardially (1 microgram). The intraocular inflammatory response induced by tumour necrosis factor was examined by slit-lamp and protein extravasation into aqueous humor was determined. The phenotype of the inflammatory cells in the eye was analysed by immunohistochemistry. In addition, the kinetics of intraocular interleukin 6 production were determined. At 24 hr after intravitreal injection, a significant clinical uveitis was observed only in rats injected with 50 ng of tumour necrosis factor, when compared to saline-treated controls (P < 0.05). Maximal clinical uveitis and blood-aqueous barrier breakdown were already present at 4 hr after tumour necrosis factor injection. The uveitis was characterized by a massive cellular infiltrate in the anterior segment, consisting predominantly of polymorphonuclear cells and macrophages/monocytes, and to a lesser extent of T lymphocytes. Intraocular interleukin 6 mRNA expression and elevated levels of interleukin 6 in aqueous humor were detected 1 hr after tumor necrosis factor injection, reached a maximum at 3 to 4 hr after injection, and had declined again at 2 hr. Although intracardial injection of 1 microgram of tumour necrosis factor in Lewis rats induced a rise of circulating interleukin 6, it did not produce uveitis. The results obtained with intravitreally injected tumour necrosis factor indicate that intraocular TNF may play a pivotal role in the induction of uveitis in the rat. The transient intraocular production of interleukin 6 early during tumour necrosis factor-induced uveitis suggests that this cytokine may participate in the response induced by tumour necrosis factor.