Mogamulizumab and bexarotene are a promising association for the treatment of advanced cutaneous T-cell lymphomas: a case series.

BACKGROUND: Treatment choices for patients with advanced-stage mycosis fungoides (MF) or Sézary syndrome (SS) who have failed first-line systemic therapies can be challenging, as several options are available. However, most evidence is based on observational and early phase studies due to the rarity of the disease. Mogamulizumab has recently been approved for the treatment of adult patients with MF or SS who have received at least one prior systemic therapy; it has a good tolerability profile prompting its use in combination with other agents. This article aims at describing the role of the concomitant use of bexarotene with mogamulizumab in this setting. CASES PRESENTATION: To add information in the field, we describe our experience with four patients with MF/SS who failed first- and second-line treatments and started the combination mogamulizumab in addition to bexarotene. The combination of bexarotene with mogamulizumab in patients with advanced MF/SS after the failure of bexarotene alone obtained a response in all the four patients observed. The response was maintained longer than expected. CONCLUSIONS: The combination is promising and deserves further study.

In Vivo reflectance confocal microscopy of cutaneous acute graft-versus-host disease: concordance with histopathology and interobserver reproducibility of a glossary with representative images.

BACKGROUND: The reliability to non-invasively identify features of inflammatory dermatoses by reflectance confocal microscopy (RCM) remains unknown. Lack of formal training among RCM readers can result in inconsistent assessments, limiting clinical utility. Specific consensus terminology with representative images is necessary to ensure consistent feature-level interpretation among RCM readers. OBJECTIVES: (1) Develop a glossary with representative images of RCM features of cutaneous acute graft-versus-host disease (aGVHD) for consistent interpretation among observers, (2) assess the interobserver reproducibility among RCM readers using the glossary, and (3) determine the concordance between RCM and histopathology for aGVHD features. METHODS: Through an iterative process of refinement and discussion among five international RCM experts, we developed a glossary with representative images of RCM features of aGVHD. From April to November 2018, patients suspected of aGVHD were imaged with RCM and subsequently biopsied. 17 lesions from 12 patients had clinically and pathologically confirmed cutaneous aGVHD. For each of these lesions, four dermatopathologists and four RCM readers independently evaluated the presence of aGVHD features in scanned histopathology slides and 1.5 × 1.5 mm RCM submosaics at 4 depths (blockstacks) respectively. RCM cases were adjudicated by a fifth RCM expert. Interobserver reproducibility was calculated by mean pairwise difference (U statistic). Concordance between modalities was determined by fraction of assignments with agreement. RESULTS: We present a glossary with representative images of 18 aGVHD features by RCM. The average interobserver reproducibility among RCM readers (75%, confidence interval, CI: 71-79%) did not differ significantly from dermatopathologists (80%, 76-85%). The concordance between RCM and histopathology was 59%. CONCLUSIONS: By using the glossary, the interobserver reproducibility among RCM readers was similar to the interobserver reproducibility among dermatopathologists. There was reasonable concordance between RCM and histopathology to visualize aGVHD features. The implementation of RCM can now be advanced in a variety of inflammatory conditions with a validated glossary and representative image set.

HIDRAdisk: validation of an innovative visual tool to assess the burden of hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory skin disease characterized by painful inflamed nodules, recurrent abscesses and fistulas located in apocrine gland-bearing body sites. The negative impact of HS on patient's quality of life (QoL) has been reported to be greater than other dermatologic conditions as psoriasis and atopic eczema, and its improvement is an important goal in disease management. Nowadays, there are no specific validated QoL instruments available for HS and generic dermatologic questionnaires are used. OBJECTIVE: The objective of this study was to demonstrate the validity, reliability and responsiveness of HIDRAdisk, a new innovative tool designed for rapid assessment of HS burden and, at the same time, an intuitive graphic visualization of the measurement outcome. METHODS: A multicentre, longitudinal, observational study was conducted to validate the HIDRAdisk compared with other validated questionnaires [Skindex-16, Dermatology Life Quality Index (DLQI), Work Productivity and Activity Impairment-General Health (WPAI:GH)] and to evaluate its correlation with disease severity in Italian patients with any degree of HS severity, as measured by Hurley stage and HS Physician Global Assessment (HS-PGA). RESULTS: A total of 140 patients (59% women; mean age 34.9 ± 11.0 years) were enrolled in 27 dermatologic centres. HIDRAdisk showed a strong correlation with Skindex-16 and DLQI, and a good one with WPAI:GH (correlation coefficient: 0.7568, 0.6651 and 0.5947, respectively) and a statistically significant correlation with both Hurley stage and HS-PGA. Very good internal consistency (Cronbach coefficient >0.80; intraclass correlation coefficient >0.6), with correlation between the 10 items, good test-retest reliability (Spearman correlation coefficient, 0.8331; P < 0.0001) and responsiveness to changes were demonstrated. CONCLUSION: Our study shows that HIDRAdisk, a short and innovative visual HS QoL instrument, has been psychometrically validated in Italian language and it may help improve the management of HS once implemented in routine clinical practice.

Sclerosing nevus with pseudomelanomatous features: dermoscopic and confocal aspects.

BACKGROUND: Sclerosing nevus with pseudomelanomatous features (SNPFs) is a clinical and pathologic entity that mimics melanoma both clinically and histologically. The lesion is a melanocytic nevus, histologically characterized by fibrosis and a pseudomelanomatous proliferation. It is typically seen in young to middle-aged individuals, mainly on the back, where microtrauma or inflammatory changes are more frequent. Dermoscopic description of SNPF has been reported so far in one case series. OBJECTIVE: The aim of our study was to describe the dermoscopic and confocal features of SNPF. METHODS: Histopathologically confirmed cases of SNPF were retrospectively collected from three referral centres in Italy. Only lesions with available clinical, dermoscopic and histopathological data were included; confocal images were also retrieved, when available. Lesions were evaluated for the presence of 12 dermoscopic and five confocal criteria previously described. RESULTS: The study population included 93 lesions in as many patients (71 men and 22 women; median age: 38 years). Dermoscopically, we found a predominance of dark colours, in particular brown and blue, which were found in all lesions and the vast majority of the lesions (86/93; 92.5%) displayed at least one structureless area. By the combination of colours and structures, we observed that the majority of the lesions (67/92; 72%) were characterized by more than one structure and more than one colour. Confocal evaluation was performed on a subset of 24/93 lesions showing a regular architecture pattern (19/24 cases, 79%), with a predominance of the ringed pattern. The presence of focal cytologic atypia at the dermal-epidermal junction was present in 12/24 cases (50%) with a prevalent dendritic-shaped cell proliferation. CONCLUSIONS: The current study demonstrated that SNPF was frequently characterized, on dermoscopic examination, by more than one structure and more than one colour and on confocal microscopy by a regular ringed pattern with focal dendritic atypical cells.

In vivo characterization of pustules in Malassezia Folliculitis by reflectance confocal microscopy and optical coherence tomography. A case series study.

BACKGROUND AND OBJECTIVE: Malassezia Folliculitis (MaF) is an inflammatory condition of hair follicles caused by Malassezia yeast. Optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) are imaging technologies enabling in vivo visualization of superficial skin layers. This study explores morphology of pustules in MaF imaged by OCT and RCM. METHODS: Patients with microscopically verified MaF were included in this case series. Morphology was evaluated qualitatively with RCM and OCT, focusing on shape, border and content of selected pustules. RESULTS: Nine patients with MaF were included. Clinically, six patients presented monomorphic MaF with multiple superficial pustules, while three patients showed more polymorph MaF appearance. In total 13 pustules were investigated by RCM and OCT. In RCM images, pustules varied from having a well-defined border with homogenous content to ill-defined borders with heterogeneous content. A distinct black halo was occasionally observed around pustules as were dilated vessels. In OCT images, pustules appeared polymorphic, showing both well- and ill-defined structures with oval or irregular shape and more or less homogenous content. Malassezia fungi were not discernible by either RCM or OCT. Specific morphological image features in RCM and OCT did not reflect different clinical manifestations of MaF. CONCLUSION: RCM and OCT images identify morphological aspects of MaF pustules, and confirm that MaF is a folliculitis with clinical as well as morphological variance.

Handheld reflectance confocal microscopy, dermatoscopy and histopathological correlation of common inflammatory balanitis.

BACKGROUND: The term balanitis includes a variety of inflammatory skin diseases involving the glans penis whose clinical diagnosis may be challenging. A biopsy is often required to obtain a definitive diagnosis, although it is barely accepted by patients. Reflectance confocal microscopy (RCM), that provides a real-time, en face imaging of the epidermis and upper dermis, is currently utilized for the diagnosis of some neoplastic and inflammatory skin diseases. The aim of this study was to analyze the RCM handheld findings of some common balanitis and to correlate them with dermatoscopy and histopathological features. MATERIALS AND METHODS: Thirty-two patients with biopsy-proven diagnosis of psoriatic balanitis (10 patients), Zoon's balanitis (11 patients) and lichen sclerosus et atrophicus (11 patients) were evaluated using a handheld RCM device and ×10 dermatoscopy. RESULTS: At the end of the study, each disorder presented specific RCM patterns that correlated with dermatoscopy and histopathological findings. CONCLUSION: The use of handheld RCM as complementary tool in everyday clinical practice for the evaluation of inflammatory diseases involving sensitive areas such as male genitalia, may contribute to reduce the need of invasive procedures.

Dermoscopy vs. reflectance confocal microscopy for the diagnosis of lentigo maligna.

BACKGROUND: Several dermoscopic and in vivo reflectance confocal microscopy (RCM) diagnostic criteria of lentigo maligna (LM)/lentigo maligna melanoma (LMM) have been identified. However, no study compared the diagnostic accuracy of these techniques. OBJECTIVE: We evaluated the diagnostic accuracy of dermoscopy and RCM for LM/LMM using a holistic assessment of the images. METHODS: A total of 223 facial lesions were evaluated by 21 experts. Diagnostic accuracy of the clinical, dermoscopic and RCM examination was compared. Interinvestigator variability and confidence level in the diagnosis were also evaluated. RESULTS: Overall diagnostic accuracy of the two imaging techniques was good (area under the curve of the sROC function: 0.89). RCM was more sensitive (80%, vs. 61%) and less specific (81% vs. 92%) than dermoscopy for LM/LMM. In particular, RCM showed a higher sensitivity for hypomelanotic and recurrent LM/LMM. RCM had a higher interinvestigator agreement and a higher confidence level in the diagnosis than dermoscopy. CONCLUSION: Reflectance confocal microscopy and dermoscopy are both useful techniques for the diagnosis of facial lesions and in particular LM/LMM. RCM is particularly suitable for the identification of hypomelanotic and recurrent LM/LMM.

Reflectance confocal microscopy analysis of equivocal melanocytic lesions with severe regression.

BACKGROUND: The differential diagnosis between regressing nevi and melanoma might be challenging; regressing areas can represent a confounding factor for the diagnosis and the histology still remain mandatory to rule out melanoma. Reflectance confocal microscopy may add valuable information by revealing features suggestive of the nature of the melanocytic proliferation. OBJECTIVE: To assess the impact of confocal microscopy in the management of regressive melanocytic lesions. METHODS: The dermoscopic analysis of 92 melanocytic lesions showing that more than 30% of regressions have been retrospectively considered, among them, 32 melanocytic lesions with a 7 check point list ≥3 they were assessed at the rcm and subsequently excised. For each selected lesion, dermoscopic features of regression (white scar-like areas, blue areas, blue white areas), distribution of regressing areas (central, peripheral, or both) and the percentage of regression have been examined by an expert in dermoscopy, blinded to the histological and confocal diagnosis. Subsequently, two experts in confocal microscopy revaluated, blinded from histology, RCM images. RESULTS: Of the 32 lesions analyzed, 23 (71.5%) were diagnosed histologically as nevi, and 9 (28.5%) as melanomas. 26 of 32 lesions (81.5%) exhibited regression >50% of the overall. On RCM, 11 lesions have been interpreted as malignant and 21 as benign. On RCM the majority of nevi exhibited regular architecture without cytological atypia. Epidermal disarray, pagetoid infiltration, disarranged dermo-epidermal junction architecture and atypical nests were considered as suspicious for malignancy. Good concordance between confocal readers has been detected. CONCLUSION: A combined dermoscopic/confocal approach can be used for the management of lesions exhibiting dermoscopic features of regression in order to provide a more conclusive pre-histological diagnosis avoiding a high number of unnecessary excisions. Limits of this study were represented by the relatively small number of lesions and the retrospective approach. Further, prospective studies on a larger number of cases, will be necessary in order to compare the efficacy of dermoscopy alone versus dermoscopy in combination with RCM for the evaluation of regression, suspected pigmented lesions.

Histopathology and reflectance confocal microscopy features of photodamaged skin and actinic keratosis.

BACKGROUND: Actinic keratosis (AK) usually co-exists in areas of severe photodamage, but the clinical applicability of reflectance confocal microscopy (RCM) in diagnosing AK currently depends on a set of parameters yet to be defined in comparison to photodamaged skin (PD). OBJECTIVE: To correlate the RCM features of PD and AK with histopathology. METHODS: Twenty participants with a mean age of 64 years and skin phototype I and II were studied. RCM was performed on two PD and one AK within a field of 25 cm2 on the left dorsal forearm, followed by shave biopsies. Blinded evaluation of the histopathological and RCM images using established parameters in AK were performed retrospectively in consensus with an expert confocalist, correlated with the histopathological diagnosis by a board-certified dermatopathologist. RESULTS: A total of 57/60 areas were included. There were 43/57 (75%) and 14/57 (25%) histopathologically confirmed PD and AK respectively. Individual corneocytes, stratum corneum disruption, dermal inflammatory cells, increased vascularity/dilated vessels and solar elastosis were detected in PD and AK upon histopathology and RCM. The features in favour of AK were parakeratosis, hyperkeratosis, more severe keratinocyte pleomorphism and architectural disruption, and the presence of epidermal inflammatory cells. PD also demonstrated keratinocyte pleomorphism and architectural disruption though this was generally less severe than AK. A small subset of PD exhibited a comparable degree of keratinocyte pleomorphism and architectural disruption to the AKs in the cohort. CONCLUSIONS: The viable epidermis demonstrates PD and AK to be part of a disease continuum corresponding to field cancerization. Individual corneocytes, stratum corneum disruption, dermal inflammatory cells, increased vascularity/dilated vessels and solar elastosis may be present in PD; whereas, parakeratosis and hyperkeratosis may represent the key to distinguishing AK from PD using RCM. The significance of epidermal inflammatory cells in the RCM diagnosis of AK remains to be elucidated.

Multicentre study on inflammatory skin diseases from The International Confocal Working Group: specific confocal microscopy features and an algorithmic method of diagnosis.

BACKGROUND: The real value of reflectance confocal microscopy (RCM) for the evaluation of inflammatory skin conditions remains unclear. A project on RCM for inflammatory skin diseases involving international centres was designed by a coordinating centre and executed under the supervision of the International Confocal Working Group. OBJECTIVES: To identify specific confocal features useful for distinction between the three main groups of superficial inflammatory skin diseases. METHODS: Nineteen different RCM features were evaluated in a total of 155 lesions, diagnosed as spongiotic (45), interface (52) or psoriasiform (58) dermatitis, collected by a consortium of 19 different centres. RESULTS: Univariate and multivariate analysis identified RCM descriptors for the three main superficial inflammatory disease groups. Later, a multivariate method was employed to define a scoring system to be applied on an algorithmic method of analysis for fast clinical application. CONCLUSIONS: Our preliminary evaluation supports the use of RCM for the identification of confocal patterns consistent with the major features of the diagnostic groups of inflammatory skin diseases. Moreover, an efficient multivariate method for clinical in vivo RCM diagnosis using a tree decision diagram has been established.

Reflectance Confocal Microscopy for Inflammatory Skin Diseases.

In vivo reflectance confocal microscopy (RCM) is a relatively novel non-invasive tool for microscopic evaluation of the skin used prevalently for diagnosis and management of skin tumour. Its axial resolution, its non-invasive and easy clinical application represents the goals for a large diffusion of this technique. During the last 15 years, RCM has been demonstrated to be able to increase the sensibility and sensitivity of dermoscopy in the diagnosis of skin tumours integrating in real time clinic, dermoscopic and microscopic information useful for the definition of malignancy. Despite to date, no large comparative studies on inflammatory skin diseases has been published in the literature, several papers already showed that RCM has a potential for the evaluation of the descriptive features of the most common inflammatory skin diseases as psoriasis, lupus erythematosus, contact dermatitis and others. The aim of the application of this technique in non-neoplastic skin diseases has been prevalently focused on the possibility of clinical diagnosis confirmation, as well as therapeutic management. Moreover, the use of RCM as driver for an optimised skin biopsy has been also followed in order to reduce the number of unsuccessful histopathological examination. In this review article we describe the confocal features of the major groups of inflammatory skin disorders focusing on psoriasiform dermatitis, interface dermatitis and spongiotic dermatitis.

Reflectance confocal microscopy for inflammatory skin diseases.

Reflectance confocal microscopy evaluation of inflammatory skin diseases represents a relatively new indication that, during the last 5 years, has shown an increasing interest with consequent progressive increment of publications in literature. The success of RCM in this filed of dermatology is directly related to the high needing of non-invasive techniques able to reduce the number of skin biopsies and support the clinical diagnosis and patient's management. RCM demonstrated to visualize microscopic descriptors of inflammatory and pigmentary skin conditions with good reproducibility between observer and high grade of correspondence with optical histology. Moreover, RCM has shown to provide sufficient data to support clinical diagnosis and differential diagnosis of inflammatory and pigmentary skin diseases. Recently, several works published in literature have opened the prospective to use RCM also for therapeutic follow-up in order to monitor the improvement of the microscopic parameters and help to prevent treatment side effects. In this review article we present some examples of RCM application in inflammatory and pigmentary diseases.

Reflectance confocal microscopy for plaque psoriasis therapeutic follow-up during an anti-TNF-α monoclonal antibody: an observational multicenter study.

BACKGROUND: Psoriasis is a chronic recurrent inflammatory skin disease that affects 2-3% of the world population. Biologics are relatively new systemic treatments that block molecular steps important in the pathogenesis of psoriasis. In vivo Reflectance confocal microscopy (RCM) is a non-invasive, imaging technique already reported to be useful in the evaluation of the follow-up of PP under treatment with topical actives and phototherapy. No reports on systemic treatments have been proposed in literature so far. OBJECTIVE: The aim of this study was to evaluate the feasibility of RCM in the monitoring of microscopic response to a subcutaneous anti-TNF treatment, Adalimumab. METHODS: One target lesion with typical clinical aspect, from 48 psoriatic patients, was evaluated using RCM at baseline, after 4 and 8 weeks of treatment. RESULTS: Microscopic confocal changes were followed up during treatment. Results disclosed identification of early microscopic evidence of the anti-inflammatory activity of Adalimumab not detected at clinical examination. Confocal feature related to the effect of TNF-α on melanocytes activity has been also identified. CONCLUSION: Early detected RCM parameters related to Adalimumab activity could be used to identify an early response to the treatment. RCM seems to be able to give useful and practical information about follow-up in patients with PP under treatment with Adalimumab.