Cutaneous melanoma in patients treated with tumour necrosis factor inhibitors: a retrospective series of 15 patients.

BACKGROUND: Several case reports suggested that tumour necrosis factor-α (TNF) inhibitors might increase the incidence and/or alter the natural course of melanoma towards a more aggressive behaviour. OBJECTIVE: Our objective was to point if history of melanoma in patients exposed to TNF inhibitors could present with a particular pattern at diagnosis or during follow-up. METHODS: We performed a retrospective multicentre study settled in the West part of France to collect and analyse all cases of patients with melanoma who received anti-TNF therapy. RESULTS: Fifteen cases were included. First, 10 patients (mean age: 55.6 years; sex ratio: 1) had a melanoma diagnosed after TNF inhibitors initiation. The mean duration between initiation of treatment and melanoma was 48.7 months. Two patients died of metastatic disease. Second, four patients had a past history of melanoma before anti-TNF therapy (mean duration of treatment: 10.8 months). None experienced a progression of melanoma disease. Last, one woman had a past history of melanoma before and then developed a second melanoma when exposed to biotherapy. CONCLUSION: Our case series does not reveal a distinct profile of melanoma in the patients exposed to TNF inhibitors. Additional prospective trials including larger number of patient are needed to demonstrate the possible link between biological therapy with TNF inhibitors and development of melanoma.

Dermoscopy of acral melanoma: a multicenter study on behalf of the international dermoscopy society.

BACKGROUND: Most studies on dermoscopy of acral lesions were conducted in Asian populations. In this study, we analyzed these features in a predominantly Caucasian population. OBJECTIVE: Estimate the prevalence of dermoscopic features in acral lesions, and assess their level of agreement between observers. METHODS: In this retrospective multicenter study, 167 acral lesions (66 melanomas) were evaluated for 13 dermoscopic patterns by 26 physicians, via a secured Internet platform. RESULTS: Parallel furrow pattern, bizarre pattern, and diffuse pigmentation with variable shades of brown had the highest prevalence. The agreement for lesion patterns between physicians was variable. Agreement was dependent on the level of diagnostic difficulty. CONCLUSION: Lesions with a diameter >1 cm were more likely to be melanoma. We found as well that a benign pattern can be seen in parts of melanomas. For this reason one should evaluate an acral lesion for the presence of malignant patterns first.

[D-penicillamine-induced pemphigus: changes in anti-32-2B immunostaining patterns]. / Autonomisation d'un pemphigus induit par la D-pénicillamine: évolution de l'immunomarquage par l'anticorps anti-32-2B.

BACKGROUND: It has been reported that D-penicillamine causes pemphigus that is typically superficial. Immunostaining with monoclonal anti-32-2B antibody targeting desmoglein 1 and 3 can help differentiate between drug-induced and classical auto-immune pemphigus. Absence of specific staining militates in favour of drug-induced pemphigus whilst positive staining suggests an auto-immune aetiology that is ongoing despite discontinuation of drug therapy. PATIENTS AND METHODS: A 59-year-old male patient was referred for management of superficial pemphigus 1 year after starting D-penicillamine treatment for scleroderma. The diagnosis of pemphigus was confirmed histologically (intra-epidermal cleavage, acantholysis and perikeratinocytes, deposition of IgG and complement C3). Immunochemical staining with anti-32-2B antibody was initially normal, in keeping with drug-induced pemphigus. Despite discontinuation of D-penicillamine, pemphigus recurred in 2008. A further skin biopsy was undertaken and anti-32-2B staining was abnormal, which is consistent with auto-immune pemphigus. DISCUSSION: Numerous cases of drug-induced pemphigus have been described in the literature. In approximately half of all cases, the pemphigus recedes after cessation of the causative drug. However, there have been no previous reports that changes over time in the immunostaining with anti-32-2B antibodies can mirror a change in form of pemphigus from a drug-induced type to an idiopathic type as well as the associated clinical feature of persistence after drug withdrawal. CONCLUSION: Normal staining with anti-32-2B antibody is associated with a favourable prognosis as regards resolution of drug-induced pemphigus. When, as in this case, status changes to abnormal staining, there is a risk that the pemphigus may become chronic despite discontinuation of therapy.

[Primitive cutaneous Ewing's sarcoma: a diagnostic and therapeutic dilemma]. / Sarcome d'Ewing cutané primitif : difficultés diagnostiques et thérapeutiques.

BACKGROUND: Ewing's sarcoma (or peripheral neuroectodermal tumour) is generally found in bone tissue, and a primary dermal site is extremely rare. We report a case of primary cutaneous Ewing's sarcoma in a 21-year-old woman. PATIENTS AND METHODS: A 21-year-old woman presented with a scapular lesion that had been slowly developing for one year. The 1-cm lesion was removed and histological examination showed proliferation of small round cells in the dermis. Immunostaining revealed cytoplasmic membrane expression of CD99 and a negative immunoprofile for other small round-cell tumors. Ewing's sarcoma fusion gene transcripts were detected using fluorescence in situ hybridization (FISH). A staging examination revealed no other abnormalities. It was decided to treat the lesion as for osseous Ewing's sarcoma with wide resection followed by systemic adjuvant chemotherapy. DISCUSSION: Cutaneous Ewing's sarcoma raises concerns about diagnosis and treatment. Owing to the non-specificity of its clinical presentation, histology and immunoprofile, diagnosis of superficial Ewing's sarcoma is difficult and numerous differential diagnoses must be considered. When dealing with a surface tumour, the diagnosis of cutaneous Ewing's sarcoma must be considered. CD99 immunostaining and molecular testing for evidence of EWSR1 rearrangement are useful investigations to confirm the diagnosis. Furthermore, modalities of treatment must be carefully discussed. Cutaneous Ewing's sarcoma is currently treated in the same way as osseous Ewing's sarcoma (wide surgical excision, adjuvant radiotherapy when surgical margins are unsatisfactory, systemic adjuvant chemotherapy, and, in some cases, bone marrow transplant). However, some studies show a more favourable prognosis for cutaneous Ewing's sarcoma than for osseous Ewing's sarcoma. We may thus ask whether such aggressive multimodal treatment is needed.

High-resolution ultrasonography assists the differential diagnosis of blue naevi and cutaneous metastases of melanoma.

BACKGROUND: Metastases of cutaneous melanoma may simulate benign blue naevi clinically. OBJECTIVES: To investigate the value of ultrasonography in the differential diagnosis of lesions that look similar clinically, i.e. blue naevi and cutaneous metastases of melanoma. METHODS: Participants were invited for inclusion in the study if they had a cutaneous blue lesion clinically suggestive of a blue naevus or cutaneous metastasis of melanoma. After obtaining signed consent, the lesion was photographed and studied using dermoscopy and high-resolution ultrasonography before being removed for histological examination. Clinical, dermoscopic and ultrasonographic images were reviewed anonymously by four dermatologists to assign the diagnosis of blue naevus or metastasis of melanoma. The diagnostic performance of clinical examination, dermoscopy and sonography was assessed for the ability of each to differentiate between metastases of melanoma and blue naevi with reference to the histological diagnosis. Moreover, experts undertook a semeiological description of each ultrasonographic image according to seven items: location of the lesion, echogenicity, homogeneity, shape of the lesion, definition of margins, posterior acoustic shadow and increased posterior echogenicity. RESULTS: Twenty-eight patients were included with a total of 39 blue skin lesions, and 17 of the 28 patients had a previous history of melanoma. Interobserver agreement in the semeiological description of the sonographic images was good (κ≥0·6) for five of seven items. Sonography was more specific (94%) than clinical examination (77%) and dermoscopy (74%). The sonographic features contributing to the differential diagnosis were: location of the lesion (P=0·027), shape of the lesion (P<0·001), homogeneity (P=0·001) and increased posterior echogenicity (P=0·007). CONCLUSIONS: Ultrasonography is a reproducible and specific tool that can assist the differential diagnosis between blue naevi and metastases of melanoma. A blue naevus is a homogeneous, hypoechoic, 'dish-shaped' lesion, located in the superficial dermis, whereas metastases of melanoma are 'potato-shaped', hypoechoic, heterogeneous lesions, located in the hypodermis.

[Absence of inferior labial or lingual frenula in Ehlers-Danlos syndrome: a new diagnostic criterion?]. / Absence de frein lingual ou labial inférieur dans le syndrome d'Ehlers-Danlos: un nouveau critère diagnostique?

BACKGROUND: Ehlers-Danlos syndrome comprises a rare and heterogeneous group of diseases affecting the skin, joints and vessels. Diagnosis is based on clinical score since molecular testing is not routinely available. High sensitivity and specificity concerning the absence of inferior labial and lingual frenula has been reported in Ehlers-Danlos syndrome, but the diagnostic value of this finding has been contested. PATIENTS AND METHODS: We here report the cases of 2 female patients, one with a vascular form of Ehlers-Danlos syndrome complicated by spontaneous dissection of the carotid and vertebral arteries, and the other with classic type; in both women, inferior labial and lingual frenula were absent. DISCUSSION: We discuss the discrepancies between the 3 published studies dealing with abnormalities of the inferior labial and lingual frenula in Ehlers-Danlos syndrome. We suggest routine oral examination in patients with suspected Ehlers-Danlos syndrome. The diagnostic value of absence of oral frenula in Ehlers-Danlos syndrome requires confirmation by a prospective study.

[Eosinophilic fasciitis associated with Borrelia burgdorferi infection]. / Fasciite à éosinophiles survenue secondairement à une infection par Borrelia burgdorferi.

BACKGROUND: Eosinophilic fasciitis (Shulman syndrome) is defined by the association of sclerodermatous skin changes involving underlying fascia and hypereosinophilia. While the aetiology is unknown, some observations suggest an infectious origin. We report the association of eosinophilic fasciitis with an infection involving Borrelia burgdorferi. PATIENTS AND METHODS: A 54 year-old man consulted for a hardened oedema and stiffness of the calves associated with an oedema of the left hand evolving for 4 months. Routine blood tests showed hypereosinophilia at 1.01 G/l and moderate inflammatory syndrome. Diagnosis of eosinophilic fasciitis was confirmed by MRI and muscle biopsy. Since the patient had reported previous tick bites some months before onset, he was tested for Lyme disease. An ELISA test revealed IgG directed against Borrelia burgdorferi and this was confirmed by Western blot analysis. DISCUSSION: The association of eosinophilic fasciitis with Lyme disease raises the question of a real link or a fortuitous association between the two conditions. Similar cases have been described in the literature with or without isolation of the spirochete from skin or fascia lesions. The incidence of eosinophilic fasciitis remains low compared to the prevalence of the infection in endemic areas. We suggest that in some patients, perhaps genetically predisposed, infection with B. burgdorferi may be at the origin of fasciitis.

[Knowledge and problems regarding the topical treatment of leg ulcers: survey among general practitioners in the Indre-et-Loire area]. / Connaissances et difficultés des médecins dans le traitement local des ulcères de jambe. Enquête auprès de médecins généralistes en Indre-et-Loire.

INTRODUCTION: The quantity of topical treatments for leg ulcers has increased over the last 15 years. OBJECTIVE: To determine the prescriptions for topical treatments and the problems in the management of leg ulcers using a questionnaire sent to general practitioners. MATERIAL AND METHODS: A questionnaire in 3 parts was sent to 95 general practitioners in the area working in 36 different districts with an explanatory letter. The first part was composed of 29 closed questions regarding prescription of topical treatment for leg ulcers. The second part, also closed, included 3 pictures showing a budding, a necrotic and a fibrinous ulcer. The physicians had to choose which treatment they would have prescribed and the frequency of dressings changes. The third part was composed of two open questions regarding the problems encountered. The survey started on May 1st and was closed on June 30th 2002. No reminders were sent. RESULTS: We received 52 replies, 49 of which were exploitable. Forty-five percent (43/95) did not reply. Occlusive dressings were widely prescribed (mainly hydrocolloid 38/49 and hydrocellular 28/49). Vaseline impregnated gauze were less prescribed (14/49). Dressings with balsam of Peru were prescribed often by 10 and occasionally by 27 general practitioners. Alginate or charcoal dressings were not always used appropriately. Antiseptics were prescribed by 10 physicians. Mechanical debridement of fibrinous or necrotic wounds was rarely used even for necrotic ulcers. Topical anesthetics were prescribed in 21 out of 33 cases of mechanical debridement. Some physicians referred care (n=4), others complained about lack of compliance (n=15), cost (n=14), local intolerance (n=10) and the excessively wide variety of dressings (n=10). We drew-up a synopsis with guidelines for treatment, which was sent to all the general practitioners who had participated in the survey. CONCLUSION: Forty-three of the 95 physicians approached did not reply. This poor response rate, which is common in this type of survey, may include physicians who are not at ease in the management of ulcers and this may bias the results. The physicians who replied to the survey knew the subject well but complained of the costs and variety of dressings. They were all eager to receive further information and guidelines.

[Becker's nevus and hemimaxillary hypoplasia: coincidence or syndrome?]. / Nævus de Becker et hypoplasie hémimaxillaire: association fortuite ou syndrome ?

INTRODUCTION: Becker's nevus is a dermatological disease sometimes associated with a malformation such as hemifacial bone dysplasia. OBSERVATION: A 11-year-old male patient presented with a delayed growth of the left maxillary and dental impactions. At 15 years of age, Becker's nevus appeared on the upper torso, both shoulders and cheeks. Le Fort I segmented osteotomy with an iliac bone graft was complicated because of maxillary dysplasia. DISCUSSION: The chronology of our patient's cutaneous and maxillary abnormalities was similar to previously reported cases. Conversely, the Becker's nevus-bone dysplasia association has been reported only twice. It may not be a coincidence and could belong to a Becker's nevus syndrome.

Can automated dermoscopy image analysis instruments provide added benefit for the dermatologist? A study comparing the results of three systems.

BACKGROUND: Instruments designed to provide computer program-driven diagnosis of dermoscopic images of lesions are now commercially available. Multiple publications tout the improved diagnostic accuracy of these instruments compared with that of clinicians. OBJECTIVES: Our aim was to evaluate the actual usefulness of these instruments for dermatologists practising in a pigmented lesion clinic. METHODS: Over a 4-month period we subjected lesions, which were being evaluated in one of our clinics, to automated computer diagnosis performed by three commercially available instruments. We intentionally included three groups of lesions: group 1 lesions were suspicious melanocytic lesions that were scheduled to be excised; group 2 lesions were nonmelanocytic lesions; group 3 lesions were clinically obvious melanomas. The automated diagnoses provided by the instruments were compared with the dermoscopy diagnosis of experienced physicians and with histopathology. RESULTS: We included a total of 107 lesions. One imaging system's computer algorithm was unable to analyse one third of the lesions. All three instruments' computer algorithms were able to identify the clinically obvious melanomas (group 3) correctly. However, all three systems tended to overdiagnose by incorrectly classifying most seborrhoeic keratoses (group 2) as potential malignant lesions. Concerning the suspect melanocytic lesions (group 1), which are precisely the lesions for which a dermatologist would welcome a second opinion, we found significant variability in the diagnostic accuracy of the instruments tested. However, all three systems providing computer-assisted diagnosis had a tendency to overdiagnose benign melanocytic lesions as potential melanomas. CONCLUSIONS: Although the image analysis systems tested by us correctly identified the clinically obvious melanomas, they were not able to discriminate between most dysplastic naevi and early malignant melanoma. Thus, for the moment these computer-assisted diagnostic imaging machines provide little to no added benefit for the experienced dermatologist/dermoscopist.

Acquired melanocytic naevus in childhood vulval pemphigoid.

BACKGROUND: Eruptive epidermolysis bullosa (EB) naevi comprise a subset of melanocytic naevi with atypical features that characteristically occur in areas of former blistering in patients suffering from hereditary EB. OBSERVATION: The case is reported of a girl who presented with pruritus, blistering and erosions of the vulval region. Clinical and immunopathological features were consistent with the diagnosis of childhood vulval pemphigoid. In the course of the disease, she developed an atypical melanocytic naevus on the left labium at a site of former blistering. Although its clinical and dermoscopic features resembled malignant melanoma, the lesion completely regressed clinically during the 24-month follow-up. CONCLUSION: This is the first report describing the development of a melanocytic naevus at sites of blistering in an auto-immune subepidermal blistering disease in childhood. Our observation extends the spectrum of disorders, in addition to the group of congenital EB, in which 'eruptive' atypical melanocytic naevi may occur. Knowledge of this complication is important for appropriate management and follow-up and to avoid radical surgery.

Is ultrasound lymph node examination superior to clinical examination in melanoma follow-up? A monocentre cohort study of 373 patients.

BACKGROUND: There is still lack of consensus regarding the most effective follow-up for stage I and II melanoma patients although some consensus conferences have provided guidelines stating that clinical examination should be the standard. OBJECTIVES: Our aim was to study the value of adding ultrasound lymph node examination (7.5 MHz) to the routine clinical examination recommended by French guidelines in melanoma follow-up. METHODS: A cohort of melanoma patients was enrolled between 1 July 1995 and 1 July 2000 in a follow-up protocol including clinical examination performed four times a year for thick melanomas (Breslow index > or = 1.5 mm) and twice a year for thin melanomas (Breslow index < 1.5 mm) according to French guidelines, and ultrasound lymph node examination performed every 6 months for thick melanomas and every year for thin melanomas. Follow-up was continued up to 1 July 2003. When clinical or ultrasound examination indicated signs of node recurrence, surgical biopsy of the involved node was performed. When ultrasound examination was only suspicious, another ultrasound examination was performed within the following 3 months. The results of both clinical and ultrasound examinations were compared with histopathology examination when node biopsy was performed. RESULTS: Ultrasound follow-up was performed for 373 patients (213 females and 160 males). Mean age at diagnosis of melanoma was 59 years (range 14-90, SD 15). In total, 1909 ultrasound examinations combined with clinical examination were analysed. Node biopsy was performed in 65 patients and demonstrated melanoma metastases in 54. Sensitivity of clinical examination and ultrasound examination was 71.4%[95% confidence interval (CI) 55.4-84.3] and 92.9 (95% CI 80.5-98.5), respectively, P = 0.02. Specificity of clinical examination and ultrasound examination was 99.6% (95% CI 99.2-99.8) and 97.8% (95% CI 97.0-98.4), respectively. Despite this apparent superiority of ultrasound examination over palpation, only 7.2% of the patients really benefited from ultrasound examination (earlier lymph node metastasis detection or avoidance of unnecessary surgery), while 5.9% had some deleterious effect from ultrasound examination (unnecessary stress caused by repetition of ultrasound examination for benign lymph nodes, useless removal of benign lymph node). CONCLUSIONS: This study confirms the greater sensitivity of ultrasound examination to clinical examination in the diagnosis of node metastases from cutaneous melanoma. However, the place of ultrasound in routine follow-up is at least questionable as only a very small proportion of patients (1.3%) really benefited from adding ultrasound examination to clinical examination.

A high prevalence of sensitization still persists in leg ulcer patients: a retrospective series of 106 patients tested between 2001 and 2002 and a meta-analysis of 1975-2003 data.

BACKGROUND: Sensitization to topical treatments used in leg ulcers is common. Questioning and patch testing are used to identify causative drugs or dressings. OBJECTIVES: To study the current frequency of sensitization in our centre, to analyse previously published studies, and to compare sensitization in recent years with studies published before 1990. METHODS: A retrospective study was undertaken of all patients admitted with leg ulcers in 2001 and 2002. Of the files of 235 patients with leg ulcers reviewed, we identified 106 patients (group A) who had been patch tested in our institution between 2001 and 2002 with the European standard series and an additional series. The frequency of sensitization was compared with an earlier unpublished retrospective study in our centre of 36 leg ulcer patients tested in 1988 (group B), with a group of unselected contact dermatitis patients tested between 1 January 1997 and 31 December 2000 in our centre (group C), and with results published in the literature. We performed a computerized database search of MEDLINE and compared results obtained in recent years with those obtained before 1990 to obtain evidence of changing trends. RESULTS: Seventy-five per cent of the 106 patients had at least one positive reaction, and 57% had two or more positive reactions. Balsam of Peru was positive in 40% of cases, followed by lanolin (21%), fragrance mix (18%), trichlocarban (13%), colophony (11%), Cetavlon (cetrimide cream) (9%) and neomycin (9%). Thirty-five of the 36 group B patients had at least one positive reaction. Lanolin was the most frequent (31%), followed by balsam of Peru (22%), Cetavlon (19%), colophony (14%), terebenthene (14%), quinoline mix (11%) and benzocaine (8%). Two hundred and eighty-six of 526 patients of group C were positive in at least one test (54.4%). Three allergens gave a sensitization rate >10%: balsam of Peru (12.5%), fragrance mix (15.2%) and nickel sulphate (21.1%). Review of the literature and calculation of sensitization rates in a pool of 3043 patients extracted from 24 series, plus our own, showed persistence of high sensitization rates and a significant (8.5%) increase in sensitization between the two periods compared. There was a decrease in sensitivity to lanolin, constant sensitization to aminoglycosides, a slight increase in sensitivity to thiuram mix and glucocorticoids, and a marked increase in sensitivity to balsam of Peru in France. Newer topical treatments and dressings showed very low rates of sensitivity with the exception of hydrogels. CONCLUSIONS: Despite warnings, sensitization to topical treatments for leg ulcers is still frequent and, moreover, continues to increase, some variations reflecting local nursing practices and variations in topical treatment available. Although a decrease in sensitization rate with lanolin has been observed throughout the world, no decrease in sensitization rate has been demonstrated with aminoglycosides, and sensitization to glucocorticoids, thiuram mix and new products (hydrogels) is now increasingly being reported.