Aberrant ETS-1 signalling impedes the expression of cell adhesion molecules and matrix metalloproteinases in non-segmental vitiligo.

Cell adhesion is a complex process that involves multiple molecules on the cell surface (ie cell adhesion molecules [CAMs]), surrounding cells and extracellular matrix (ECM). Repigmentation in vitiligo is dependent on the ECM remodelling and cellular migration, primarily attributed to the transcriptional activation of matrix metalloproteinases (MMPs). In this study, we aimed to demonstrate the role of ETS-1 signalling in the regulation of MMPs and CAMs. Therefore, we studied the expression of ETS-1, MMPs (MMP-2, MMP-9) and CAMs including E-cadherin, ITGA-1 and ICAM-1 in vitiligo (both active and stable) ex vivo. Further, we compared melanocyte morphology and their adhesion towards collagen IV and laminin between control and vitiligo groups in vitro. Also, we silenced ETS-1 in melanocytes cultured from control skin and observed post-silencing effect on above-mentioned MMPs and CAMs. We perceived absent ETS-1 and significantly reduced CAMs and MMPs in vitiligo compared with normal skin. Scanning electron microscopy (SEM) revealed a translucent material surrounding individual melanocytes in stable vitiligo and controls, whereas active vitiligo melanocytes demonstrated loss of this extracellular substance. Adhesion assays revealed significantly decreased binding of cultured melanocytes to collagen IV and laminin V plates in both stable and active vitiligo. Importantly, ETS-1 silencing resulted in significantly reduced expression of CAMs and MMPs. In conclusion, absent ETS-1 expression in both stable and active non-segmental vitiligo seems to impede the expression of CAMs, apart from MMPs, probably leading to progressive depigmentation in active disease and absence of spontaneous repigmentation in stable disease.

Therapeutic success of tofacitinib in granuloma annulare: A retrospective case series of 15 patients.

Background Granuloma annulare (GA) is a necrobiotic granulomatous disorder that may sometimes be resistant to treatment, especially the generalised form. Tofacitinib has recently shown promise in the treatment of non-infective granulomatous dermatosis. Objectives In this study, we aimed to evaluate the response of generalised GA to oral tofacitinib. Methods This was a retrospective case series in patients of generalised GA who were treated with oral tofacitinib 5 mg twice a day in a tertiary care centre in north India. Baseline clinical details and histopathological findings were reviewed. Treatment response was noted in the form of clearance of lesions (complete or partial) along with the time taken to achieve the maximum response. Results A total of 15 patients of generalised GA were included in this study, amongst whom nine patients were resistant to conventional therapies whilst the remaining were treatment naïve. Complete clearance of lesions was noted in 11 patients at a mean treatment duration of 4.4 ± 2.1 months whereas clearance was partial in four, with a mean follow-up duration post- treatment in patients who had partial clearance, which is 7.3 ± 2.8 month, with a reduction in erythema and infiltration in those lesions. Adverse effects in the form of hyperlipidemia were observed in two patients. Conclusion Tofacitinib, a JAK-STAT inhibitor is beneficial in treating GA, especially in those with generalised and recalcitrant disease.

Unusual clinical presentations in leprosy: a case series and review.

Conventionally, leprosy has been divided into various spectra of presentation ranging from the tuberculoid to the lepromatous pole, as well as histoid, pure neuritic leprosy and reactional states. This however is an oversimplification as leprosy can present in unusual clinical forms that may obfuscate the diagnosis. Our objective was to highlight unusual clinical presentations of leprosy occurring across all spectra of the disease. Our case series describes eight uncommon presentations of leprosy seen over a period of 10 y from 2011 to 2021, wherein clinical diagnosis followed by a histopathological confirmation of leprosy was performed. These include rare presentations such as psoriasiform plaques, Lazarine leprosy, verrucous plaques and hypertrophic scarring. Many of these rare presentations remain hitherto unreported, such as primary hypogonadism and annular plaques mimicking erythema annulare centrifugum and erythema gyratum repens. Sarcoidosis and syphilis have been labeled as great mimickers in dermatology. The current case series and review is an attempt to highlight a multitude of unusual presentations of leprosy that need a separate mention to make a correct and timely diagnosis and prevent the debilitating sequelae of this otherwise treatable infectious disease.

Contiguous squamous proliferations in syringocystadenoma papilliferum: A retrospective study of 14 cases.

BACKGROUND: Syringocystadenoma papilliferum is a benign adnexal neoplasm. Contiguous squamous proliferation has been rarely described in syringocystadenoma papilliferum. AIMS: This study aimed to evaluate the spectrum and pathogenesis of contiguous squamous proliferation in syringocystadenoma papilliferum. MATERIALS AND METHODS: All cases of syringocystadenoma papilliferum diagnosed over the past 12 years were screened for contiguous squamous proliferation. Cases with associated nevus sebaceous were excluded from the study. Immunohistochemistry for GATA3, CK7, BRAFV600E and p16 was performed. PCR for human papilloma virus, type 16 and 18, was carried out. RESULTS: Of a total of 30 cases, 14 cases showed associated contiguous squamous proliferation which included four cases of verrucous hyperplasia, six cases with papillomatosis, two cases with mild squamous hyperplasia and one case each of Bowen's disease and squamous cell carcinoma. In the cases with non-neoplastic contiguous squamous proliferations, the squamous component did not express CK7 or GATA3. However, the squamous component of premalignant and malignant lesions expressed CK7 and GATA3 concordant with the adenomatous component. BRAF was positive in adenomatous component in five cases while the contiguous squamous proliferation component was negative for BRAF in all but one case. p16 was negative in both components of all cases and PCR for human papilloma virus was negative in all cases. LIMITATIONS: Due to the rarity of disease, the sample size of our study was relatively small with two cases in the 2nd group, that is, syringocystadenoma papilliferum with malignant contiguous squamous proliferation. Detailed molecular studies such as gene sequencing were not performed. CONCLUSION: Syringocystadenoma papilliferum with contiguous squamous proliferation is underreported, and most commonly displays verrucous hyperplasia. The premalignant and malignant contiguous squamous proliferations likely arise from syringocystadenoma papilliferum while the hyperplastic contiguous squamous proliferations likely arise from the adjacent epidermis. Relationship with high-risk human papilloma virus is unlikely. However, further molecular analysis of larger number of cases is required to establish the pathogenesis.

International Dermoscopy Society criteria for non-neoplastic dermatoses (general dermatology): validation for skin of color through a Delphi expert consensus.

BACKGROUND: The International Dermoscopy Society (IDS) recently released a set of five basic dermoscopic parameters (vessels, scales, follicular findings, "other structures," and specific clues) encompassing a total of 31 subitems to standardize the use of dermoscopy in non-neoplastic dermatoses, yet they have been developed taking into account Caucasian/Asian skin, with consequent possible limitations if used in dark skin. OBJECTIVES: To validate the abovementioned criteria for the use in dark-skinned patients (phototypes IV-VI) through an expert consensus. METHODS: The two-round Delphi method was adopted, with an iterative process consisting of two rounds of email questionnaires. Potential panelists were recruited via e-mail from all over the world based on their expertise on dermoscopy of non-neoplastic dermatoses in skin of color. RESULTS: Twenty-two panelists took part in the validation process. All of the five originally proposed parameters and subitems reached agreement during the first round, aside from "follicular red dots." Additionally, during round 1, five new subitems were proposed (perifollicular scales distribution, follicular openings obliteration, broken hairs, eccrine pigmentation, and eccrine ostia obliteration), along with the possibility to change the denomination of parameter 3 (from "follicular findings" to "follicular/eccrine findings") and split it into two subparameters ("follicular findings" and "eccrine findings"). All such proposals reached agreement during the second round and therefore were included in the final list, for a total of 37 items. CONCLUSIONS: Although nearly all the dermoscopic criteria originally proposed by the IDS are applicable even to darker phototypes, several additional variables need to be assessed.

Dermoscopy in general dermatology (non-neoplastic dermatoses) of skin of colour: a comparative retrospective study by the International Dermoscopy Society.

BACKGROUND: Dermoscopy has been shown to be a useful supportive tool to assist the diagnosis of several non-neoplastic dermatoses (i.e. inflammatory, infiltrative and infectious skin diseases), yet data on skin of colour is still limited. OBJECTIVES: To characterize dermoscopic features of non-neoplastic dermatoses in dark-skinned patients in order to identify possible clues that may facilitate the differential diagnosis of clinically similar conditions. MATERIALS & METHODS: Members of the International Dermoscopy Society were invited to submit cases of any non-neoplastic dermatosis developing in patients with Fitzpatrick Phototypes V-VI whose diagnosis had been confirmed by the corresponding gold standard diagnostic test. A standardized assessment of the dermoscopic images and a comparative analysis according to clinical presentation were performed. Seven clinical categories were identified: (I) papulosquamous dermatoses; (II) facial hyperpigmented dermatoses; (III) extra-facial hyperpigmented dermatoses; (IV) hypopigmented dermatoses; (V) granulomatous dermatoses; (VI) sclerotic dermatoses; and (VII) facial inflammatory dermatoses. RESULTS: A total of 653 patients (541 and 112 with Phototype V and VI, respectively) were recruited for the analysis. Thirty-six statistically significant dermoscopic features were identified for papulosquamous dermatoses, 24 for facial hyperpigmented disorders, 12 for extra-facial hyperpigmented disorders, 17 for hypopigmented disorders, eight for granulomatous dermatoses, four for sclerotic dermatoses and 17 for facial inflammatory diseases. CONCLUSION: Our findings suggest that dermoscopy might be a useful tool in assisting the diagnosis of clinically similar non-neoplastic dermatoses in dark phototypes by revealing characteristic clues. Study limitations include the retrospective design, the lack of a direct dermoscopic-histological correlation analysis and the small sample size for less common diseases.