French guidelines for the management of oral lichen planus (excluding pharmacological therapy).

INTRODUCTION: Oral lichen is a chronic inflammatory disease for which diagnostic management and follow-up are heterogeneous given the absence of specific guidelines in France. Our objective was to develop French multidisciplinary guidelines for the management of oral lichen. MATERIALS AND METHODS: Working groups from the Groupe d'Etude de la Muqueuse Buccale (GEMUB) formulated a list of research questions and the corresponding recommendations according to the "formal consensus" method for developing practice guidelines. These recommendations were submitted to a group of experts and the degree of agreement for each recommendation was assessed by a scoring group. RESULTS: Twenty-two research questions, divided into 3 themes (nosological classification and initial assessment, induced oral lichenoid lesions, and follow-up) resulted in 22 recommendations. Initial biopsy for histology is recommended in the absence of reticulated lesions. Biopsy for direct immunofluorescence is recommended for ulcerated, erosive, bullous types and for diffuse erythematous gingivitis. Management should include a periodontal and dental check-up, and investigation for extra-oral lesions. Hepatitis C testing is recommended only if risk factors are present. Definitions, triggering factors and the management of "induced oral lichenoid lesions" were clarified. Oral lichen must be monitored by a practitioner familiar with the disease at least once a year, using objective tools. CONCLUSION: This formalised consensus of multidisciplinary experts provides clinical practice guidelines on the management and monitoring of oral lichen.

Topical rapamycin versus betamethasone dipropionate ointment for treating oral erosive lichen planus: a randomized, double-blind, controlled study.

BACKGROUND: Although superpotent topical corticosteroids are the first-line treatment for oral erosive lichen planus (OELP), topical rapamycin was found efficient in a previous case series. OBJECTIVES: To compare the efficacy and safety of topical rapamycin and betamethasone dipropionate ointment for OELP in a randomized, double-blind trial. METHODS: Patients were randomized to receive treatment with betamethasone dipropionate ointment 0.05% in Orabase® or topical rapamycin solution (1 mg/mL) on lesions twice daily for 3 months, followed by 3 months of observation. The primary outcome was clinical remission after 3 months of treatment. Secondary outcomes were clinical remission after 1 and 2 months, reduced oral pain and reduced impact on food intake after 3 months, clinical recurrence after treatment withdrawal, and adverse events. RESULTS: During a 4-year period, 76 patients were randomized and 75 received treatment (rapamycin, n = 39; betamethasone, n = 36). At 3 months, 39.4% of patients with betamethasone and 27.3% with rapamycin showed clinical remission (odds ratio 0.68, 95% CI [0.24; 1.89]; P = 0.46). Rates of remission after 1 and 2 months, reduction in pain and impact on food intake after 3 months, were higher with betamethasone than rapamycin. Recurrence of oral erosions was similar between groups. Adverse events occurred in 43.6% of patients with rapamycin (mostly burning sensation, impaired taste) and 27.8% with betamethasone (mostly oral candidiasis). CONCLUSION: Although the study was limited by insufficient recruitment, we did not find any superiority of topical rapamycin over betamethasone dipropionate ointment for OELP. Given the rapid remission and pain improvement in the betamethasone group, it appears that superpotent topical corticosteroids should remain the first-line treatment for OELP.

High-frequency ultrasound quantification of acute radiation dermatitis: pilot study of patients undergoing radiotherapy for breast cancer.

BACKGROUND: Acute radiation dermatitis (ARD) is a frequent complication after breast cancer radiotherapy and is usually assessed by semi-quantitative clinical scores, which may be subject to inter-observer variability. High-frequency ultrasound imaging of the skin can reliably quantify thickness and edema in diseased skin. We aimed to compare the relative increase in dermal thickness of the irradiated zone in breast-cancer patients undergoing radiotherapy, with clinical severity. METHODS: A consecutive series of patients undergoing treatment for breast cancer by lumpectomy and radiotherapy in a 6-month period also underwent clinical and ultrasound evaluation of ARD. RESULTS: We included 34 female patients 17 had grade 1 (group 1), 17 had grade 2 or grade 3 ARD (group 2). The mean relative increase in dermal thickness in irradiated skin (RIDTIS) was greater for group 2 than 1: 0.53 vs 0.29 mm (P=.023). On univariate analysis, ARD was associated with skin phototype, breast volume and RIDTIS, and on multivariable analysis, breast volume and age remained predictive of the disease. CONCLUSION: Patients with more severe dermatitis showed significantly increased dermal thickness. Dermal thickness is a quantitative variable that could help quantify the efficacy of drugs and improve the treatment of this disease in patients undergoing radiotherapy.

Focal role of tolerability and reasonableness in the radiological protection system.

The concepts of tolerability and reasonableness are at the core of the International Commission on Radiological Protection (ICRP) system of radiological protection. Tolerability allows the definition of boundaries for implementing ICRP principles, while reasonableness contributes to decisions regarding adequate levels of protection, taking into account the prevailing circumstances. In the 1970s and 1980s, attempts to find theoretical foundations in risk comparisons for tolerability and cost-benefit analysis for reasonableness failed. In practice, the search for a rational basis for these concepts will never end. Making a wise decision will always remain a matter of judgement and will depend on the circumstances as well as the current knowledge and past experience. This paper discusses the constituents of tolerability and reasonableness at the heart of the radiological protection system. It also emphasises the increasing role of stakeholder engagement in the quest for tolerability and reasonableness since Publication 103.

Early Low Urinary CXCL9 and CXCL10 Might Predict Immunological Quiescence in Clinically and Histologically Stable Kidney Recipients.

We monitored the urinary C-X-C motif chemokine (CXCL)9 and CXCL10 levels in 1722 urine samples from 300 consecutive kidney recipients collected during the first posttransplantation year and assessed their predictive value for subsequent acute rejection (AR). The trajectories of urinary CXCL10 showed an early increase at 1 month (p = 0.0005) and 3 months (p = 0.0009) in patients who subsequently developed AR. At 1 year, the AR-free allograft survival rates were 90% and 54% in patients with CXCL10:creatinine (CXCL10:Cr) levels <2.79 ng/mmoL and >2.79 ng/mmoL at 1 month, respectively (p < 0.0001), and 88% and 56% in patients with CXCL10:Cr levels <5.32 ng/mmoL and >5.32 ng/mmoL at 3 months (p < 0.0001), respectively. CXCL9:Cr levels also associate, albeit less robustly, with AR-free allograft survival. Early CXCL10:Cr levels predicted clinical and subclinical rejection and both T cell- and antibody-mediated rejection. In 222 stable patients, CXCL10:Cr at 3 months predicted AR independent of concomitant protocol biopsy results (p = 0.009). Although its positive predictive value was low, a high negative predictive value suggests that early CXCL10:Cr might predict immunological quiescence on a triple-drug calcineurin inhibitor-based immunosuppressive regimen in the first posttransplantation year, even in clinically and histologically stable patients. The clinical utility of this test will need to be addressed by dedicated prospective clinical trials.

[Frequency of lymphoscintigraphic anomalies in the contralateral limb and progression of unilateral primary lymphedema in children]. / Fréquence des anomalies lymphoscintigraphiques infracliniques controlatérales et évolution des lymphœdèmes primaires unilatéraux de l'enfant.

BACKGROUND: Primary lymphoedema (LE) is the consequence of lymphatic insufficiency, usually associated with hypoplasia of the lymph vessels and/or nodes. Lymphoscintigraphy allows early diagnosis. OBJECTIVES: To assess the frequency of contralateral LE by lymphoscintigraphy in children with unilateral primary LE of one limb; to assess facets of clinical bilateralization of LE. METHODS: This retrospective single-centre study included children with unilateral LE followed up at the Tours university hospital centre between 2004 and 2014. Parents were contacted by phone to obtain follow-up data. RESULTS: Of the 13 children included, 6 (46%) displayed bilateral lymphatic anomalies on lymphoscintigraphy. Within a median follow-up period of 6 years, clinical bilateralization was observed in one girl after progression of her LE for 7 years; in her case, bilateral lymphatic insufficiency was detected at the initial lymphoscintigraphy. CONCLUSION: While contralateral subclinical lymphatic insufficiency is frequent in children with unilateral primary LE of the limbs, clinical bilateralization appears only rarely.

Serial lymphoscintigraphic findings in a patient with Gorham's disease with lymphedema.

Gorham's disease is a rare disorder characterized by vascular, "lymphangio- matous" and/or "hemangiomatous" lesions in bone and surrounding soft tissues. Associated lymphedema has not been reported and clinical evolution is unpredictable. Plain radiographs, CT, MRI, and occasionally bone scintigraphy, are used to detect the bone and soft tissues changes. Biopsy is a major component of the diagnostic process. We report the findings of serial lymphoscintigraphy in a young boy with a polyostotic Gorham's disease associated with lymphangioma of the thigh and lower limb lymphedema. In this patient, lymphoscintigraphy was useful for diagnosis and follow-up of primary lymphedema. It provided valuable information concerning the occurrence, location, and progression of lymphatic lesions in both bone and soft tissues.

Prospective multicentre observational study of lymphedema therapy: POLIT study.

OBJECTIVE: Lymphedema treatment is based on Decongestive Lymphedema Therapy (DLT) with an intensive phase followed by a long-term maintenance phase. This study aimed to observe volume variation over the intensive phase and 6 months later. METHODS: Prospective multicentre observational study of patients with unilateral lymphedema. The primary objective was to assess lymphedema volume variation between baseline, the end of intensive phase and 6 months later. Secondary objectives were to assess the frequency of heaviness limiting limb function and treatments safety predictors for volume reduction. RESULTS: Three hundred and six patients (89.9% women; 59.9±14.3 years old) with upper/lower (n=184/122) limb lymphedema were included. At the end of the intensive phase, median excess lymphedema volume reduction was 31.0% (41.7-19.9) followed by a 16.5% (5.9-42.3) median increase over the 6-month maintenance period phase. Previous intensive treatment was the only significant predictor of this response. As compared to baseline, heaviness limiting limb use was much less frequently reported at the end of the reductive phase (75.5% versus 42.3% respectively), and was more frequent at the end of the maintenance phase (62.6%). The most frequent adverse events reported were skin redness and compression marks (18.4 and 15.7% of patients, respectively). Blisters requiring treatment stoppage were rare (1.4%). CONCLUSIONS: Intensive phase decreases lymphedema volume and heaviness limiting limb function. The benefit is partially abolished after the first 6 months of maintenance. There is a need to consider how to provide optimal patient care for the long-term control of lymphedema.

[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.

Contributions of SPECT/CT imaging to the lymphoscintigraphic investigations of the lower limb lymphedema.

Lymphoscintigraphy is a safe and reliable technique for investigating lymphedema. However, interpretation of delayed planar conventional imaging may be questionable due to the superimposition of soft tissues. Therefore, the aim of this retrospective study was to evaluate the contribution of single photon emission computed tomography/computed tomography (SPECT/CT) to lymphoscintigraphic investigation in a selected population with abnormal interstitial activity. Forty one patients with lower limb lymphedema either primary (n=17) or secondary (n=5), or associated with chronic venous insufficiency (n=19) underwent lymphoscintigraphy according to a standard protocol. SPECT/CT imaging that started immediately after planar imaging covered the part of the lower limbs with the most significant interstitial activity. The CT images were also analyzed separately to identify the typical honeycomb pattern of lymphedema. SPECT/CT identified additional abnormalities in vessels and soft tissues in 19 patients (46%). The additional information, primarily related to dermal collateralization of flow, dermal backflow, lymphangioma, and lymphorrhea, aided in understanding the physiopathology of edema and may have influenced management in 35 patients (85%). The honeycomb appearance of the soft tissues was noted on CT in most patients (90%). This study suggests that SPECT/CT is a promising addition to planar imaging in lymphoscintigraphic investigations of lymphedema.

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.

[Limb lymphedema: Diagnosis, explorations, complications. French Lymphology Society]. / Les lymphoedèmes des membres: diagnostic, explorations, complications.

Lymphedema results from impaired lymphatic transport with increased limb volume. Primary and secondary forms can be distinguished. Secondary lymphedema of the upper limb is the most frequent in France. A 2-cm difference on any segment of the limb confirms the diagnosis of lymphedema. Calculated lymphedema volume using the formula for a truncated cone is required to assess the efficacy of treatment and to monitor follow-up. Primary lymphedema is sporadic but rarely familial. Lymphoscintigraphy is useful in the primary form to evaluate precisely lymphatic function of the two limbs. Erysipelas is the main complication,but psychological or functional discomfort may occur throughout the course of lymphedema. Lipedema is the main differential diagnosis, defined as an abnormal accumulation of fat from hip to ankle and occurs almost exclusively in obese women.

[High-resolution ultrasonography: utility in diagnosis, treatment, and monitoring dermatologic diseases]. / L'échographie cutanée haute résolution: utilité pour le diagnostic, le traitement et la surveillance des maladies dermatologiques.

Although less precise than histological examination, high-resolution skin imaging is a noninvasive technique that provides complementary information to the clinical examination: the lesion's US structure as well as its lateral and depth extension. Ultrasonography helps in diagnosis and initial management by measuring melanoma thickness (so as to remove this lesion with safety margins) before destructive treatment (cryosurgery or radiotherapy), by showing tumor limits, or by detecting subclinical recurrence during the follow-up. In this paper, ultrasound images will be correlated with clinical and histological data in various clinical situations such as tumors, edema, cutaneous infiltration, sclerous tissues, hyperlaxity, and cutaneous aging.

[Acquired bullous diseases of the oral mucosa]. / Maladies bulleuses acquises de la muqueuse buccale.

Bullous diseases of the oral cavity cause painful erosion. They must be distinguished from aphthae and vesicles which may have a similar presentation. Acute, chronic and congenital conditions are recognized. Acute lesions may involve a polymorphous oral erhythema which has an polymorphous erythematous presentation or toxidermia (Stevens-Johnson syndrome, Lyell syndrome, fixed pigmented erythema). Examination of the skin and history taking are the keys to diagnosis. Patients with chronic bullous diseases may have a congenital condition (bullous epidermolysis or lymphangioma) suggested by the age at onset and the clinical presentation. Acquired chronic bullous diseases include lichen planus and autoimmune bullous diseases. Careful examination is essential to identify mucosal or cutaneous involvement and to obtain a biopsy for histological examination. Search for antibodies deposited in the perilesional mucosa is necessary. Chronic erosive gingivitis is a frequent presentation. Most of the patients have cicatricial pemphigoid, lichen planus, and more rarely pemphigus. The pinch sign is highly discriminative to differentiate the cause of this syndrome. Symptomatic treatment of bullous lesions of the oral cavity include adapted diet and correct and early use of antalgesics.

[Paraneoplastic pemphigus revealing dendritic cell sarcoma originating from Castleman's disease of the neck]. / Pemphigus paranéoplasique révélateur du développement d'un sarcome à cellules dendritiques à partir d'une tumeur de Castleman pulmonaire.

INTRODUCTION: Paraneoplastic pemphigus is associated with Castleman's disease. We report a case of paraneoplastic pemphigus at the stage of the sarcomatous transformation of Castleman's disease, present for many years but without concomitant paraneoplastic pemphigus. The pemphigus was manifested by the most unusual, exclusive, involvement of the mucosa of the mouth and lung. OBSERVATION: A 32 year-old man suffering from extensive ulceration of the oral mucosa was hospitalized in December 2000 for alteration in his general status of health and acute respiratory failure. The search for intercellular anti-substance antibodies on rat spleen was positive, corresponding to anti-envoplakin IgG and leading to the diagnosis of paraneoplastic pemphigus. The thoracic x-ray and scan revealed a hilum tumor, the histological examination of which confirmed the diagnosis of Castleman's disease concomitant to sarcomatous transformation. Following surgical treatment, the respiratory failure worsened. The patient improved with systemic corticosteroids at the dose of 2 mg/kg/d and chemotherapy was initiated. The patient died suddenly within the context of acute respiratory failure, three months after surgery. DISCUSSION: This is a case of paraneoplastic pemphigus of unusual clinical and biological expression: exclusively mucosal involvement with obliterating bronchiolitis, explained by the isolated presence of antibodies recognizing envoplakin, without anti-desmoglein. The transformation of the Castleman tumor into a sarcoma may have unmasked intra-cellular antigens (plakins), initiating the specific immune reaction.

Intralesional therapy with anti-CD20 monoclonal antibody rituximab: local and systemic efficacy in primary cutaneous B-cell lymphoma.

Rituximab (MabThera, Roche) is a chimeric monoclonal antibody directed against the CD20 antigen. Its efficacy and safety were first demonstrated in the treatment of systemic B-cell lymphomas. We report the use of intralesional injections of rituximab into some but not all cutaneous lesions in a patient with multiple primary cutaneous follicular centre B-cell lymphoma. This treatment resulted in tumour regression, even of the lesions that had not been injected. We therefore hypothesize that there is systemic diffusion of rituximab from injected sites despite the low doses injected locally, or the induction of a specific antitumour immune response acting systemically.

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.