Correlation of serum level of squamous cell carcinoma antigen with severity of cutaneous psoriasis, assessed using the simplified psoriasis index.

BACKGROUND: Squamous cell carcinoma antigen (SCCA) is a biomarker of disease progression in squamous cell carcinoma but also contributes to the pathogenesis of psoriasis. Eight previous studies have shown a correlation between psoriasis severity, assessed using the Psoriasis Assessment Severity Index or body surface area, and serum level of SCCA, mainly SCCA2, assessed by means of non-commercial tests. We examined the correlation between serum SCCA level, measured with a commercial kit, and psoriasis severity assessed using the Simplified Psoriasis Index (SPI). METHODS: We conducted a prospective, non-interventional, single-centre study at the University Hospital of Tours over 18 months. The primary endpoint was same-day measurement of serum SCCA level and the psoriasis severity score on the professional version of the SPI (proSPI-s) at both baseline and follow-up. Secondary endpoints were same-day measurement of serum SCCA level and the proSPI psychosocial score (proSPI-p), proSPI treatment score, Dermatology Life Quality Index (DLQI), and inflammation parameters (C-reactive protein level, neutrophil-to-lymphocyte ratio). RESULTS: We included 50 psoriasis patients. Serum SCCA level was correlated with the proSPI-s at baseline and follow-up (Spearman r = 0.686 and r = 0.674, p < 0.0001) for both. It was correlated with the proSPI-p and DLQI. Serum SCCA level was not correlated with either neutrophil-to-lymphocyte ratio (r = 0.083) or C-reactive protein level (r = 0.192). CONCLUSION: This study is the first to correlate serum SCCA level with proSPI-s. Moreover, SCCA was measured using a widely available kit. SCCA may be used to assess the severity of psoriasis.

Rituximab is an effective treatment in patients with pemphigus vulgaris and demonstrates a steroid-sparing effect.

BACKGROUND: Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing steroid-related adverse events (AEs) is unproven. OBJECTIVES: To utilize data collected in a French investigator-initiated, phase III, open-label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV. METHODS: This was an independently conducted post hoc analysis of the moderate-to-severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0·5 or 1·0 mg kg-1 per day prednisone tapered over 3 or 6 months, or 1·0 or 1·5 mg kg-1 per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24-month efficacy and safety results were also reported. RESULTS: At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab-plus-prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS-related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone. CONCLUSIONS: In patients with moderate-to-severe PV, rituximab plus short-term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life-threatening CS-related AEs. What's already known about this topic? Pemphigus vulgaris (PV) is the most common type of pemphigus. Corticosteroids, a standard first-line treatment for PV, have significant side-effects. Although their effects are unproven, adjuvant corticosteroid-sparing agents are routinely used to minimize steroid exposure and corticosteroid-related side-effects. There is evidence that the anti-CD20 antibody rituximab is effective in the treatment of patients with severe recalcitrant pemphigus and in patients with newly diagnosed pemphigus. What does this study add? This study provides a more detailed analysis of patients with PV enrolled in an investigator-initiated trial. Rituximab plus prednisone had a steroid-sparing effect and more patients achieved complete remission off prednisone. Fewer patients experienced grade 3 or grade 4 steroid-related adverse events than those on prednisone alone. This collaboration between academia and industry, utilizing independent post hoc analyses, led to regulatory authority approvals of rituximab in moderate-to-severe PV.

Skin cancers in patients of skin phototype V or VI with xeroderma pigmentosum type C (XP-C): A retrospective study.

BACKGROUND: Xeroderma pigmentosum (XP) is a rare genetic disease comprising 7 subgroups, A to G, all of which are associated with early onset of several forms of skin cancer. Our main objective was to determine the prevalence of skin cancers in a cohort of dark-skinned XP-C patients in Mayotte. PATIENTS AND METHODS: A single-centre cohort consisting of all XP patients was followed in the island of Mayotte from December 2015 to May 2017 by dermatologists from the University Hospital of Saint-Denis (Reunion) during the course of dermatological missions. RESULTS: Eighteen patients of median age 12.9 years (7 female/11 male) belonging to 14 families were included. All had XP-C and carried the same mutation. Median age at clinical diagnosis of XP was 1.8 years. A total of 144 skin cancers (94 squamous cell carcinomas [SCC], 30 basal cell carcinomas [BCC], 14 melanomas, 5 sarcomas and 1 sarcomatoid carcinoma) were observed in 11 of the 18 patients (61%). Eleven patients (61%) had at least 1 SCC, 6 (33%) had at least 1 BCC, 6 (33%) had at least 1 melanoma, and 4 (22%) had at least 1 sarcoma. In all, 95.5% of the cancers occurred in light-exposed skin areas. Median age was 5.4 years for the initial cancer and 6.4 years for the second. SCCs and sarcomas occurred earlier than CBCs and melanomas (P<0.0001). All patients had mild to severe poikiloderma and presented photophobia, and 50% had pigmented palmoplantar lesions. One-third had oral mucosal involvement while 78% had ocular or palpebral lesions. Nail and hair involvement was recorded in 17% of patients. The median sun protection score (evaluated on a 7-item scale) was 6/7. The median score on the quality-of-life questionnaire (DLQI) was 4/30. Severity of poikiloderma was significantly correlated with the occurrence of skin cancers. DISCUSSION AND CONCLUSION: Our cohort showed a high prevalence of skin cancer in XP-C patients of phototype V and VI exposed to UV radiation in a tropical region. SCCs were the most common tumours. The prevalence of melanoma was high, with major risk compared to controls of the same skin phototype. In addition, we found a high prevalence of sarcomas (5 patients). Initial cancers occurred early (5.4 years) compared to data from the literature, and SCCs and sarcomas occurred significantly sooner than melanomas and BCCs.

T-cell papulosis associated with B-cell malignancy: a distinctive clinicopathologic entity.

BACKGROUND: A distinctive eruption referred to as 'insect bite-like reaction' or 'eosinophilic dermatosis of haematological malignancy' has been described during the course of haematological B-cell malignancies (BCM). However, its clinical evolution, histopathological features and pathogenesis remain unclear. OBJECTIVES: To characterize this eruption and to investigate its pathogenesis and relationship with the underlying BCM. METHODS: In this multicenter retrospective study of the French Study Group on Cutaneous Lymphomas, 37 patients with a BCM and a cutaneous eruption consisting in chronic and/or recurrent papules, papulo-vesicles and/or nodules were included. Clinical, histopathological, immunohistochemical and molecular data were reviewed. RESULTS: No significant insect bite history or seasonal predominance was recorded. Patients had pruritic papules (81%), papulo-vesicles (43%) and nodules (38%), often predominated in the head and neck region (84%), without complete remission periods in most cases (57%). The predominant associated BCM was chronic lymphocytic leukaemia (73%). Histological and immunohistochemical review showed a dense dermal lymphocytic infiltrate predominantly composed of T lymphocytes (100%), with frequent eosinophils (77.6%); a perivascular and periadnexal (most often folliculotropic) pattern (77.6%), sometimes suggestive of a folliculotropic mycosis fungoides; clusters of tumour B cells were identified in 47% of cases using appropriate phenotyping markers. In 10/14 cases (71.4%) tested for B-cell IgH gene rearrangement, a B-cell clone was identified in skin lesions (identical to the blood clone in nine cases), whereas no T-cell clone was present. CONCLUSION: We propose the denomination 'T-cell papulosis associated with B-cell malignancy' (TCP-BCM) for this distinctive eruption. Although resulting in various histopathological pictures, it can be easily recognized by clinicians and may be identified by informed pathologists relying on some key features. An extravasation of tumour B cells with skin-homing properties associated with a secondary, predominant, T-cell immune reaction could explain the clinicopathologic aspect and the prolonged regressive and recurrent course of the disease.

[Paraneoplastic pemphigus: Retrospective study of a case series]. / Étude rétrospective d'une série de pemphigus paranéoplasiques.

CONTEXT: Paraneoplastic pemphigus (PNP) is a rare condition associated with poor prognosis. It associates polymorphic mucocutaneous manifestations with neoplasia. Diagnosis is difficult because of the various clinical and histological features involved and the lack of specificity of immunological examinations. METHODS: We retrospectively analyzed the records of patients presenting with PNP in the Poitou-Charentes region between 2000 and 2015. RESULTS: Seven patients were included. They presented 9 neoplasias (1 lymphoma, 1 melanoma, and 7 carcinomas) diagnosed from 4 months before to 25 months after the occurrence of cutaneous (6/7) and/or mucosal (6/7) polymorphic lesions. Histological examination revealed epidermal acantholysis (7/7), keratinocytic necrosis (4/7), and interface lichenoid dermatitis (5/7). Intercellular deposits of IgG and C3 or along the dermo-epidermal junction were detected with direct immunofluorescence (IF) (7/7). Four of 6 patients tested had positive indirect IF on rat bladder epithelium. Follow-up ranged from 1-132 months with a one-year survival of 85.7%. DISCUSSION: The clinical and histopathological presentations observed in our patients were polymorphic, with overlap between the clinical and histological features of PNP and classical pemphigus. Prognosis and survival appear better in our series than in the literature. It is possible that in some cases, the association of pemphigus with neoplasia was fortuitous, which might account for the better prognosis. A new consensus on the diagnostic criteria for PNP is needed to help practitioners to consensually diagnose it for prognostic or therapeutic trials.

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.

High neutrophil to lymphocyte ratio measured before starting ipilimumab treatment is associated with reduced overall survival in patients with melanoma.

BACKGROUND: There is an unmet need to identify markers predictive of response to ipilimumab in patients with melanoma because the number of responders to ipilimumab is low and its cost is very high. An increase in absolute lymphocyte count (ALC) or low neutrophil/lymphocyte ratio (NLR) just before the third infusion has been reported to be associated with better overall survival (OS). OBJECTIVES: Our aim was to determine whether NLR measured before the first infusion was associated with OS. PATIENTS AND METHODS: Data were collected on a consecutive series of 58 patients treated with ipilimumab in four hospitals, including 51 at stage M1c and four at stage M1b. The influences of the NLR and other factors such as lactate dehydrogenase (LDH), performance status, ALC, absolute neutrophil count (ANC) and corticosteroids on survival were studied. We also assessed this association with NLR categorized as a binary variable. The cut-off value for the NLR was determined with time-dependent receiver operating characteristic (ROC) analysis. Univariate and multivariate analyses were performed using Cox regression models. RESULTS: High NLR (≥) 4, high ANC LDH levels (>2), performance status ≥2, symptomatic brain metastases, and corticosteroids before week 1 were associated with poorer survival on univariate analysis. Using multivariate analysis, a significant association between high NLR (continuous variable) and poorer survival was demonstrated and remained significant after adjustment on potential confounders [hazard ratio (HR) = 1·21, 95% confidence interval (CI) 1·07-1·36]. NLR ≥4 was an independent prognostic factor (HR = 2·2, 95% CI 1·01-4·78). Intake of corticosteroids before week 1 was not an independent prognostic factor (HR = 1·28, 95% CI 0·54-3·06). CONCLUSIONS: High NLR (≥4) before initiating ipilimumab treatment in patients with metastatic melanoma is an independent prognostic indicator of poor survival.

[Dual localisation of ischaemic fasciitis with local relapse at one site]. / Une double localisation de fasciite ischémique avec récidive locale sur un des sites.

INTRODUCTION: Ischaemic fasciitis (IF) is a rare pseudosarcomatous proliferation initially described on the pressure points of long-term bedridden patients. Healing is the rule after surgical excision. No multifocal localisations have been reported to date. Herein, we describe the case of a patient with FI affecting two sites and having recurred at one of them. OBSERVATION: A 50-year-old woman with scoliosis and mental retardation consulted for a hard skin lesion next to her right scapula. Elastofibroma was diagnosed on the basis of a surgical biopsy sample. Early local recurrence led to a second resection four months later. Histologically, central fibrinoid necrosis was observed, surrounded by collagenous tissue containing occasionally atypical fibroblasts and numerous capillaries. The diagnosis of ischaemic fasciitis was made by a national expert. Six months later, we observed a 13-cm purplish erythematous infiltrated mass with a 6-cm ulceration at the surgical site. A second 6-cm non-ulcerated indurated purplish lesion was visible next to the right greater trochanter. The scan showed deep soft-tissue infiltration with subfascial extension and contact with the greater trochanter. Superficial biopsies of both lesions showed only an appearance of granulation tissue. MRI performed after five months showed an extension of lesions at the two sites with an appearance evocative of ischaemic fasciitis. Surgical excision was refused by the patient and her family. DISCUSSION: We report a rare case of ischaemic fasciitis at two separate sites with local relapse after surgical excision.

Frequency and prognostic value of cutaneous molecular residual disease in mycosis fungoides: a prospective multicentre trial of the Cutaneous Lymphoma French Study Group.

BACKGROUND: Monoclonal T-cell receptor (TCR) rearrangement is detected in 57-75% of early-stage mycosis fungoides (MF) at diagnosis. A retrospective study showed molecular residual disease (MRD) in 31% of patients in complete clinical remission (CR) after 1 year of treatment. OBJECTIVES: To confirm the frequency of MRD at 1 year and to determine its prognostic value for further relapse. METHODS: Patients with T1-, T2- or T4-stage MF were prospectively included in this multicentre study. At diagnosis, clinical lesions and healthy skin were biopsied. After 1 year of topical treatment, previously involved skin of patients in CR was biopsied for histology and analysis of TCR-γ gene rearrangement. The results were compared with the clinical status each year for 4 years. RESULTS: We included 214 patients, 133 at T1, 78 at T2 and three at T4 stage. At diagnosis, 126 of 204 cases (61·8%) showed TCR clonality in lesional skin. After 1 year, 83 of 178 patients (46·6%) still being followed up were in CR and 13 of 63 (21%) showed MRD. At 4 years, 55 of 109 patients (50·5%) still being followed up were in CR and 44 of 109 (40·4%) were in T1 stage. MRD did not affect clinical status at 4 years (CR vs. T1/T2, P = 1·0; positive predictive value 36·4%; negative predictive value 67·6%). CONCLUSIONS: T-cell clonality at diagnosis and MRD at 1 year are not prognostic factors of clinical status at 4 years.

Measurement of skin thickness and skin elasticity to evaluate the effectiveness of intensive decongestive treatment in patients with lymphoedema: a prospective study.

BACKGROUND: Complex decongestive physiotherapy (CDP) is used to treat patients with severe lymphoedema. The efficacy of CDP is usually quantified by calculating limb volume from repeated measurements of circumference at least 10 points before and after treatment of an affected limb. Measurement is time-consuming and operator-dependent. OBJECTIVES: To determine whether decreased dermal thickness is correlated with decreased volume after intensive CDP. METHODS: A consecutive series of patients admitted for intensive CDP were studied over a 6-month period. Before and after CDP, we measured circumference, dermal thickness elasticity and finally improvement in quality of life using a visual analogue scale (VAS). RESULTS: Thirty patients were included in the study. Only three patients were previously untreated. The average relative reduction in limb volume was 4% and the reduction in the dermal thickness was 15% (correlation: r = 0.37, P = 0.05). Viscoelasticity was decreased by 13%. VAS quality of life score was improved by 30%. CONCLUSION: Changes in dermal thickness are slightly correlated with volume changes before and after 5-day intensive CDP in a selected series of patients previously treated at home.

Vitamin D deficiency is associated with greater tumor size and poorer outcome in Merkel cell carcinoma patients.

BACKGROUND: Merkel cell polyomavirus has been recognized to be associated with Merkel cell carcinoma (MCC), but the evolution of this cancer probably depends on various factors. Vitamin D deficiency, defined by serum 25-hydroxyvitamin D levels <50 nmol/L, seems to influence cancer behavior and progression, but has never been assessed in MCC patients. OBJECTIVES: First, to evaluate whether vitamin D deficiency was associated with tumor characteristics and prognosis in a cohort of MCC patients. Second, to assess expression of the vitamin D receptor (VDR) in MCC tumors. METHODS: Clinical findings, Merkel cell polyomavirus markers and vitamin D status were assessed in a cohort of French MCC patients. The study was limited to the 89 patients for whom the serum sample had been collected within 3 years after the diagnosis of MCC. Correlation between vitamin D deficiency and MCC characteristics and outcome were determined in regression analyses. VDR expression in MCC tumours was assessed by immunohistochemistry. RESULTS: Vitamin D deficiency was noted in 65.1% of the patients and was independently associated with greater tumor size at diagnosis (P = 0.006) and with metastasis recurrence (HR, 2.89; 95% CI, 1.03 to 8.13; P = 0.043), but not with death from MCC, although there was a trend (HR, 5.28; 95% CI, 0.75 to 36.96; P = 0.093). VDR was found to be strongly expressed in all 28 MCC tumor specimens investigated. CONCLUSION: The association between vitamin D deficiency and MCC characteristics and outcome, together with detection of the VDR in MCC cells, suggest that vitamin D could influence the biology of MCC.

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.

[Mastitis revealing Churg-Strauss syndrome]. / Mastite révélatrice d'un syndrome de Churg-Strauss.

BACKGROUND: Churg-Strauss syndrome often involves the skin, and this may sometimes reveal the disease. OBSERVATION: A 25-year-old woman was referred to a gynaecologist for inflammation of the right breast with breast discharge. Cytological analysis of the liquid showed numerous inflammatory cells, particularly polymorphonuclear eosinophils and neutrophils. Ultrasound examination of the breast was consistent with galactophoritis. CRP was normal, and hypereosinophilia was seen. The patient was subsequently referred to a dermatology unit. Skin examination revealed inflammation of the entire breast, which was painful, warm and erythematous; the border was oedematous with blisters. Necrotic lesions were also present on the thumbs and knees. Skin biopsy of the breast showed a dermal infiltrate with abundant infiltrate of polymorphonuclear eosinophils, including patchy necrosis and intraepidermal vesicles. Histological examination of a biopsy sample from a thumb revealed eosinophilic granuloma and leukocytoclastic vasculitis. The patient was also presenting asthma, pulmonary infiltrates and mononeuropathy at L3, consistent with Churg-Strauss syndrome. DISCUSSION: Breast involvement in Churg-Strauss syndrome is very rare (only one other case has been reported). This is the first case in which the breast condition revealed the disease. Cutaneous involvement of the breast is, however, also compatible with Wells' cellulitis. The lesions quickly disappeared with 1mg/kg/d oral prednisolone.

[Cutaneous mucormycosis caused by Rhizopus microsporus]. / Mucormycose cutanée à Rhizopus microsporus.

BACKGROUND: Mucormycosis are rare fungal infections occurring chiefly in the lung or the rhinocerebral compartment, particularly in patients with immunodeficiency or mellitus diabetes. We report the case of an elderly patient with cutaneous mucormycosis caused by Rhizopus microsporus. PATIENTS AND METHODS: An 89-year-old man presented a skin lesion of the forearm rapidly becoming inflammatory and necrotic. The patient had been treated for 2months with oral corticosteroids for idiopathic thrombocytopenia. Histological and mycological examination of the skin biopsy revealed the presence of a filamentous fungus, R. microsporus. The outcome was unfavorable, despite prescription of high-dose liposomal amphotericin B. DISCUSSION: Mucormycosis are infrequent opportunistic infections caused by angio-invasive fungi belonging to the Mucorales order. Cutaneous presentations are rare, and in rare cases the species R. microsporus is isolated in clinical samples. Diagnosis is based on histological examination highlighting the characteristic mycelium within infected tissue, together with ex vivo mycological identification using morphological and molecular methods. Treatment consists of liposomal amphotericin B combined with debridement surgery. CONCLUSION: R. microsporus is a marginal fungal species rarely isolated in clinical practice, and even less in dermatology departments. This clinical case report highlights the severity of infection with this fungus, particularly in the absence of early surgery.

Patients' acceptance of medical photography in a French adult and paediatric dermatology department: a questionnaire survey.

BACKGROUND: Despite the increasing use of medical photography by dermatologists, no study on patients' perceptions of photography in dermatology has been performed to date. OBJECTIVES: Firstly, to evaluate patients' perceptions of medical photography. Secondly, to assess whether perceptions differed between patients in our adult department and parents accompanying a child in our paediatric department. METHODS: An opinion survey was conducted at the Hospital of Tours (France) among adult patients (adult department) and accompanying parents (paediatric department) by completion of a questionnaire after any medical photography had been performed. RESULTS: We collected 272 questionnaires regarding 158 adults and 114 children. A camera used only in the department, and storage of the images in the department's records were the most accepted modalities (> 90%), especially in the paediatric survey. Respondents agreed with the sharing of the images with other practitioners and in medical meetings (> 85%) rather than distribution via publications (58·3%), e-mails (45·5%), health magazines (44·3%) and websites (32·0%). Most (78·8%) considered that the consent form should list all the possible uses of the images. Need for renewed consent for each use of the images was significantly more often expressed in the paediatric than the adult survey (44·5% vs. 24·5%, P = 0·001). More than 95% of respondents considered medical photography to be useful for improving diagnosis, monitoring of skin disease and aiding teaching. CONCLUSIONS: These findings could be used to improve practice, to increase the acceptability of medical photography and for devising a standardized consent form for medical practitioners performing medical photography.